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Sample records for plasma renin increased

  1. Plasma renin is increased in young rats exposed to lead in utero and during nursing

    Energy Technology Data Exchange (ETDEWEB)

    Victery, W.; Vander, A.J.; Schoeps, P.; Germain, C.

    1983-01-01

    Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 5, 25, 100, or 500 ppm Pb (as Pb acetate); they were sacrificed at 1 month of age, at which time their mean blood Pb concentrations were, respectively, approximately 3, 9, 19, 30, and 70 ..mu..g/dl. All Pb-exposed groups sacrificed by decapitation had elevated mean plasma renin activities (PRA), relative to controls. Pentobarbital-anesthesia and laparotomy markedly increased PRA in the 0, 100, and 500 ppm groups, but the increase was significantly less in the 100 ppm group. Renal renin concentration was normal in the 5 and 25 ppm groups, but was significantly increased in the 100 and 500 ppm groups. The ratio of plasma angiotensin II to PRA was normal in the 100 ppm group but significantly reduced in the 500 ppm group. We conclude that exposure of rats to those generally present in human populations stimulates basal renin secretion in 1-month-old rats, but partially inhibits the response to renin-releasing stimuli. The highest dose reduces plasma angiotensin II at any given PRA. These results, taken with previous publications, emphasize that the effects of lead on plasma renin even within a single species are greatly affected by the timing of the exposure.

  2. Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

    Science.gov (United States)

    O'Malley, K; Velasco, M; Wells, J; McNay, J L

    1975-01-01

    A study was made of the possible mechanism(s) underlying minoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol. Minoxidil lowered mean arterial pressure 31.6 plus or minus 3.3 mm Hg, mean plus or minus SEM. There was an associated increase in both PRA, 6.26 plus or minus 2.43 NG/ML/H, and heart rate, 21.4 plus or minus 2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1 plus or minus 1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil. Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism(s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure. PMID:1127099

  3. Increase of plasma renin activity in male and female rabbits subjected to dysbaric conditions

    Science.gov (United States)

    Chryssanthou, C.; Kircikoglu, H.; Strugar, J.

    1985-01-01

    The renin-angiotensin-aldosterone system may be implicated in hemodynamic alterations occurring in dysbaric disorders. This report concerns changes in plasma renin activity (PRA) induced by exposure of rabbits to a compression-decompression schedule that does not normally produce clinical manifestations of decompression sickness. The results revealed a significant increase in PRA in 19 of 23 animals following dysbaric exposure. Mean PRA rose from 1.18 ng ang I/ml hr (preexposure) to 2.40 ng ang I/ml hr (postexposure). The increase was particularly pronounced in female animals (217 percent). Asymptomatic intravascular gas bubbles (silent bubbles) were detected by gross or microscopic examination in the majority of the animals. Renin elaboration and secretion in asymptomatic dysbaric exposures may be mediated by bradykinin and/or prostaglandins released or activated in a chain reaction triggered by silent gas bubbles. This hypothesis is also applicable to increased PRA in altitude decompression. Alternatively elevation of PRA may result from decreased renal perfusion when dysbaric disorders are complicated by significant hypovolemia.

  4. Improved immunoradiometric assay for plasma renin

    NARCIS (Netherlands)

    J. Deinum (Jacob); F.H.M. Derkx (Frans); M.A.D.H. Schalekamp (Maarten)

    1999-01-01

    textabstractBACKGROUND: Our renin IRMA overestimated renin in plasmas with high prorenin-to-renin ratios. We suspected that the overestimation of renin was caused less by cross-reactivity of the renin-specific antibody with prorenin than by a conformational change of pr

  5. Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); L. Tarnow; J.M. van Gool (Jeanette); R.J.A. de Bruin (René); F.H.M. Derkx (Frans); M.A.D.H. Schalekamp (Maarten); H.H. Parving

    1999-01-01

    textabstractBackground. The most striking abnormality in the renin-angiotensin system in diabetic nephropathy (DN) is increased plasma prorenin. Renin is thought to be low or normal in DN. In spite of altered (pro)renin regulation the renin gene has not been studied for contribution to the

  6. Plasma soluble (pro)renin receptor is independent of plasma renin, prorenin, and aldosterone concentrations but is affected by ethnicity.

    Science.gov (United States)

    Nguyen, Geneviève; Blanchard, Anne; Curis, Emmanuel; Bergerot, Damien; Chambon, Yann; Hirose, Takuo; Caumont-Prim, Aurore; Tabard, Sylvie Brailly; Baron, Stéphanie; Frank, Michael; Totsune, Kazuhito; Azizi, Michel

    2014-02-01

    A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mellitus, 41 hypertensive patients with or without renin-angiotensin system blockers, 9 patients with primary aldosteronism, and 10 patients with Gitelman syndrome. Median physiological plasma sPRR concentration was 23.5 ng/mL (interquartile range, 20.9-26.5) under usual uncontrolled sodium diet. sPRR concentration in healthy subjects, unlike renin and prorenin, did not display circadian variation or dependence on age, sex, posture, or hormonal status. sPRR concentrations were ≈25% lower in black than in white subjects, whereas renin concentrations were ≈40% lower. Patients with diabetes mellitus (average renin-high prorenin levels) and with hypertension only (average renin-average prorenin levels) had sPRR concentrations similar to healthy subjects. Renin-angiotensin system blockade was associated with increase of sPRR concentration by ≈12%. sPRR in patients with primary aldosteronism (low renin-low prorenin) and Gitelman syndrome (high renin-high prorenin) were similar and ≈10% higher than in healthy subjects. There was no correlation between sPRR and renin or prorenin. In conclusion, our results show that plasma sPRR concentrations are dependent on ethnicity and independent of renin, prorenin, and aldosterone concentrations in healthy subjects and in patients with contrasted degrees of renin-angiotensin system activity.

  7. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement

    DEFF Research Database (Denmark)

    Campbell, Duncan J; Nussberger, Juerg; Stowasser, Michael

    2009-01-01

    BACKGROUND: Measurement of plasma renin is important for the clinical assessment of hypertensive patients. The most common methods for measuring plasma renin are the plasma renin activity (PRA) assay and the renin immunoassay. The clinical application of renin inhibitor therapy has thrown...... are susceptible to renin overestimation due to prorenin activation. In addition, activity assays performed with peptidase inhibitors may overestimate the degree of inhibition of PRA by renin inhibitor therapy. Moreover, immunoassays may overestimate the reactive increase in plasma renin concentration in response...

  8. Renal haemodynamics and plasma renin in patients with essential hypertension.

    Science.gov (United States)

    Pedersen, E B; Kornerup, H J

    1976-05-01

    1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects. 2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients. 3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group. 4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance. 5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release.

  9. Increased plasma aldosterone-to-renin ratio is associated with impaired left ventricular longitudinal functional reserve in patients with uncomplicated hypertension.

    Science.gov (United States)

    Choi, Eui-Young; Ha, Jong-Won; Yoon, Se-Jung; Shim, Chi-Young; Seo, Hye-Sun; Park, Sungha; Ko, Young-Guk; Kang, Seok-Min; Choi, Donghoon; Rim, Se-Joong; Jang, Yangsoo; Chung, Namsik

    2008-03-01

    Relative aldosterone excess is associated with endothelial dysfunction and higher incidence of end organ damage. We sought to investigate whether plasma aldosterone-to-renin ratio (ARR) is associated with left ventricular (LV) longitudinal function reserve to exercise in patients with controlled hypertension. In the patients with controlled and uncomplicated hypertension without overt LV hypertrophy, plasma aldosterone concentrations (ng/dL) and renin activities (ng/mL/h) were measured. Then 28 consecutive patients with higher ARR (group II, ARR > or = 30, 55 +/- 10 years) and 56 age- and sex-matched patients with lower ARR (group I, ARR reserve at 25-W and 50-W exercise, defined as DeltaE' (change from resting E', cm/s) of group II was significantly lower than that of group I (2.60 +/- 1.42 vs 1.85 +/- 1.44 cm/s, P = .016; 3.40 +/- 1.48 vs 2.36 +/- 1.43 cm/s, P = .003, respectively). In conclusion, in patients with hypertension without overt LV hypertrophy, increased ARR is associated with increased LV mass, and impaired LV longitudinal functional reserve during exercise.

  10. Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake

    OpenAIRE

    Atchison, Douglas K.; Westrick, Elizabeth; Szandzik, David L.; Gordish, Kevin L; Beierwaltes, William H.

    2012-01-01

    Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-...

  11. New sensitive direct radioimmunoassay for human plasma renin and its clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Higaki, J.; Ogihara, T.; Imai, N.; Kumahara, Y.; Hontani, S.; Nishiura, M.; Ogawa, H.; Hirose, S.; Murakami, K.

    1984-12-01

    A new sensitive direct radioimmunoassay for human plasma renin has been developed. Renin was purified from Haas' preparation utilizing a pepstatin-C/sub 6/-Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from this assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation, but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension was not significantly different from values in normal controls. The values were higher in patients with renovascular hypertension, malignant hypertension and Bartter's syndrome, but lower in patients with primary aldosteronism than in normal controls. 20 references, 7 figures.

  12. Plasma Renin Activity in Diabetes Mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Pyo, Heui Jung; Park Jung Sik; Kim, Sung Kwon; Choi, Kang Won; Lee, Jung Sang; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    To evaluate the renin-angiotensin-aldosterone system in diabetes mellitus, basal plasma renin activity (PRA) and its response to intravenous furosemide were determined in 40 diabetic subjects. The diabetics were divided into 4 groups according to the presence of nephropathy and/or hypertension. Uncomplicated diabetics (Group I) were taken as control group and the results of the other groups were compared to this group. In diabetics with nephropathy alone (Group II), and with nephropathy and hypertension (Group III), basal PRA values were 0.63+-0.59 ng/ml/hr., and 0.79+-0.62 ng/ml/hr., respectively, both significantly lower than control group. (1.53+-1.09 ng/ml/hr.). (p<0.05) In both of the above groups, the responses to intravenous furosemide tended to be blunted. On the other hand, in diabetics, with hypertension only (Group IV), the basal and stimulated PRA were not significantly different from control. Above results suggests that nephropathy may be one of the factors which suppress renin activity in diabetes mellitus

  13. Plasma renin and outcome in the community : data from PREVEND

    NARCIS (Netherlands)

    de Boer, Rudolf A.; Schroten, Nicolas F.; Bakker, Stephan J. L.; Mahmud, Hasan; Szymanski, Mariusz K.; van der Harst, Pim; Gansevoort, Ron T.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Hillege, Hans L.

    2012-01-01

    The reninangiotensin system plays a central role in patients with established cardiovascular (CV) disease, but the prognostic effect of plasma renin in the community is unclear. The relationship between plasma renin concentration and CV events was studied in 6228 subjects who were enrolled in the Pr

  14. The ratios of aldosterone / plasma renin activity (ARR) versus aldosterone / direct renin concentration (ADRR).

    Science.gov (United States)

    Glinicki, Piotr; Jeske, Wojciech; Bednarek-Papierska, Lucyna; Kruszyńska, Aleksandra; Gietka-Czernel, Małgorzata; Rosłonowska, Elżbieta; Słowińska-Srzednicka, Jadwiga; Kasperlik-Załuska, Anna; Zgliczyński, Wojciech

    2015-12-01

    Primary aldosteronism (PA) is estimated to occur in 5-12% of patients with hypertension. Assessment of aldosterone / plasma renin activity (PRA) ratio (ARR) has been used as a screening test in patients suspected of PA. Direct determination of renin (DRC) and calculation of aldosterone / direct renin concentration ratio (ADRR) could be similarly useful for screening patients suspected of PA. The study included 62 patients with indication for evaluation of the renin-angiotensin-aldosterone system and 35 healthy volunteers. In all participants we measured concentrations of serum aldosterone, plasma direct renin, and PRA after a night's rest and again after walking for two hours. The concentrations of aldosterone, direct renin, and PRA were measured by isotopic methods (radioimmunoassay (RIA) / immunoradiometric assay (IRMA)). Correlations of ARR with ADRR in the supine position were r = 0.9162, r(2) = 0.8165 (p 80% and 100%, respectively) appeared for the ratios ≥ 30. We suggest that for practical and economic reasons ARR can be replaced by ADRR.

  15. Characterization of inactive renin from human kidney and plasma. Evidence of a renal source of circulating inactive renin.

    OpenAIRE

    Hsueh, W A; Carlson, E J; Dzau, V J

    1983-01-01

    An inactive form of renin has been isolated from human plasma. It has been suggested that this may represent renin precursor secreted from the kidney. However, early studies failed to isolate inactive renin from human renal tissue. In this investigation, rapid processing of human kidney cortex at temperatures below 4 degrees C in the presence of protease inhibitors followed by cibacron-blue affinity chromatography allowed us to extract a totally inactive form of renal renin. Furthermore, we f...

  16. Plasma catecholamines and renin activity in wrestlers following vigorous swimming.

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    Vigas, M; Celko, J; Juránková, E; Jezová, D; Kvetnanský, R

    1998-01-01

    Cardiovascular and neuroendocrine responses to exercise in a physically fit and an untrained group of young healthy subjects were compared to study the significance of physical fitness for performance in a discipline for which the athletes were not trained. Ten wrestlers of national rank prepared for an international competition (age 18 years) and 9 untrained healthy males (age 21 years). Exercise consisted of 27-min swimming, freestyle, in water of 29 degrees C, with last 3 min increased to maximal effort. The blood pressure, heart rate and sublingual temperature were measured and blood samples were withdrawn before exercise, immediately after and after a 30 min period of rest. Catecholamines were analyzed by radioenzymatic method and plasma renin activity (PRA) using commercial kits. Systolic blood pressure and heart rate after swimming were increased comparably in the two groups, diastolic pressure was unchanged in the controls and decreased in the wrestlers. Plasma cortisol remained unchanged. Plasma glucose tended to increase in the controls and so decrease in wrestlers, with a significant difference between them after swimming (p < 0.05). However, plasma adrenaline was concomitantly increased in both groups (p < 0.01). Noradrenaline and PRA were increased after swimming in both the control and trained group. The increments of noradrenaline and PRA in wrestlers were significantly reduced compared to the control group (p < 0.01, p < 0.05, respectively). Higher physical fitness in athletes significantly reduced plasma noradrenaline and angiotensin responses to maximal exercise demanding special skill in work performance which had not been included in their training program. Training of wrestlers did not cause an exaggerated plasma adrenaline response to exercise.

  17. Guanfacine in essential hypertension: Effect on blood pressure, plasma noradrenaline concentration and plasma renin activity

    OpenAIRE

    Schoeppe, W.; Brecht, H. M.

    1980-01-01

    1 The acute and chronic effects of guanfacine on blood pressure, plasma noradrenaline concentration and plasma renin activity were investigated in 23 patients (15 males, 8 females) with essential hypertension (WHO grade I-II).

  18. Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells.

    Science.gov (United States)

    Desch, Michael; Schreiber, Andrea; Schweda, Frank; Madsen, Kirsten; Friis, Ulla G; Weatherford, Eric T; Sigmund, Curt D; Sequeira Lopez, Maria Luisa; Gomez, R Ariel; Todorov, Vladimir T

    2010-03-01

    We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)gamma stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPARgamma. The mouse renin gene is regulated by PPARgamma through a distal enhancer direct repeat closely related to consensus PPAR response element (PPRE). In vitro studies demonstrated that PPARgamma knockdown stimulated PPRE-driven transcription. These data predicted that deficiency of PPARgamma would upregulate mouse renin expression. Consistent with these observations knockdown of PPARgamma increased the transcription of a reporter gene driven by the mouse renin PPRE-like motif in vitro. To study the impact of PPARgamma on renin production in vivo, we used a cre/lox system to generate double-transgenic mice with disrupted PPARgamma locus in renin-producing juxtaglomerular (JG) cells of the kidney (RC-PPARgamma(fl/fl) mice). We provide evidence that PPARgamma expression was effectively reduced in JG cells of RC-PPARgamma(fl/fl) mice. Fluorescent immunohistochemistry showed stronger renin signal in RC-PPARgamma(fl/fl) than in littermate control RC-PPARgamma(wt/wt) mice. Renin mRNA levels and plasma renin concentration in RC-PPARgamma(fl/fl) mice were almost 2-fold higher than in littermate controls. Arterial blood pressure and pressure control of renal vascular resistance, which play decisive roles in the regulation of renin production were indistinguishable between RC-PPARgamma(wt/wt) and RC-PPARgamma(fl/fl) mice. These data demonstrate that the JG-specific PPARgamma deficiency results in increased mouse renin expression in vivo thus corroborating earlier in vitro results. PPARgamma appears to be a relevant transcription factor for the control of renin gene in JG cells.

  19. Increased renal renin content in mice lacking the Na+/H+ exchanger NHE2.

    Science.gov (United States)

    Hanner, Fiona; Chambrey, Régine; Bourgeois, Soline; Meer, Elliott; Mucsi, István; Rosivall, László; Shull, Gary E; Lorenz, John N; Eladari, Dominique; Peti-Peterdi, János

    2008-04-01

    Macula densa (MD) cells express the Na(+)/H(+) exchanger (NHE) isoform NHE2 at the apical membrane, which may play an important role in tubular salt sensing through the regulation of cell volume and intracellular pH. These studies aimed to determine whether NHE2 participates in the MD control of renin synthesis. Renal renin content and activity and elements of the MD signaling pathway were analyzed using wild-type (NHE2(+/+)) and NHE2 knockout (NHE2(-/-)) mice. Immunofluorescence studies indicated that NHE2(-/-) mice lack NHE3 at the MD apical membrane, so the other apical NHE isoform has not compensated for the lack of NHE2. Importantly, the number of renin-expressing cells in the afferent arteriole in NHE2(-/-) mice was increased approximately 2.5-fold using renin immunohistochemistry. Western blotting confirmed approximately 20% higher renal cortical renin content in NHE2(-/-) mice compared with wild type. No-salt diet for 1 wk significantly increased renin content and activity in NHE2(+/+) mice, but the response was blunted in NHE2(-/-) mice. Renal tissue renin activity and plasma renin concentration were elevated three- and twofold, respectively, in NHE2(-/-) mice compared with wild type. NHE2(-/-) mice also exhibited a significantly increased renal cortical cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase (mPGES) expression, indicating MD-specific mechanisms responsible for the increased renin content. Significant and chronic activation of ERK1/2 was observed in MD cells of NHE2(-/-) kidneys. Removal of salt or addition of NHE inhibitors to cultured mouse MD-derived (MMDD1) cells caused a time-dependent activation of ERK1/2. In conclusion, the NHE2 isoform appears to be important in the MD feedback control of renin secretion, and the signaling pathway likely involves MD cell shrinkage and activation of ERK1/2, COX-2, and mPGES, all well-established elements of the MD-PGE(2)-renin release pathway.

  20. Plasma prolactin, renin and catecholamines in young normotensive and borderline hypertensive subjects.

    Science.gov (United States)

    Saito, I; Takeshita, E; Saruta, T; Nagano, S; Sekihara, T

    1984-02-01

    It has been reported that patients with essential hypertension have high plasma prolactin levels and suggested that reduced central dopaminergic activity may be a factor in the pathogenesis of essential hypertension. This study examines the influence of posture on plasma prolactin, plasma catecholamines, plasma renin activity, blood pressure and heart rate in 24 patients with borderline hypertension (age 19 +/- 1 years) and 20 normotensive subjects matched for age and body mass index. Supine plasma prolactin levels were similar in both groups [borderline hypertension, 11.3 +/- 0.7 ng/ml; normotensive, 10.7 +/- 0.8 ng/ml (mean +/- s.e.m.)] and no increase in plasma prolactin was observed after 10 min standing in both groups. Normotensive and borderline hypertensive subjects had similar values for supine and upright plasma renin activity and plasma norepinephrine. There were no significant correlations between supine plasma prolactin and supine blood pressure, supine plasma renin activity or plasma norepinephrine when data from both normotensive and borderline hypertensive subjects were combined. These results may provide indirect evidence against the occurrence of reduced central dopaminergic activity in borderline hypertension.

  1. Effect of oral labetalol on plasma catecholamines, renin and aldosterone in patients with severe arterial hypertension.

    Science.gov (United States)

    Kornerup, H J; Pedersen, E B; Christensen, N J; Pedersen, A; Pedersen, G

    1979-11-01

    Arterial blood pressure and plasma catecholamines, renin activity and aldosterone concentration in 12 patients with severe essential hypertension were studied before and after combined alpha- and beta-adrenergic receptor blockage induced by oral labetalol treatment for 2 months. Furosemide in a fixed dose was employed as a basic antihypertensive agent throughout the study. Blood pressure was adequately controlled in only 6 patients. Mean body weight increased by 1.8 kg and there was a rise in body weight which was inversely correlated with the fall in standing mean blood pressure. The mean plasma noradrenaline concentration decreased from 0.30 to 0.20 ng/ml, whereas plasma adrenaline did not change significantly. Plasma renin activity and aldosterone concentration varied greatly, but the mean values did not change significantly. Change in body weight was correlated inversely with changes in plasma noradrenaline and renin. The results suggest that labetalol, through its combined alpha- and beta-adrenergic receptor blocking action, induces a rise in body weight, probably due to sodium and fluid retention, which partly counterbalances the antihypertensive effect of labetalol, and partly modifies both renin and sympathetic nervous activity.

  2. Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S. (Medical Center for Postgraduate Education, Warsaw (Poland))

    1990-01-01

    Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly.

  3. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man

    Science.gov (United States)

    Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.

    1981-01-01

    The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

  4. Plasma renin responses to mental stress and carotid intima-media thickness in black Africans: the SABPA study.

    Science.gov (United States)

    Hamer, M; Malan, L; Schutte, A E; Huisman, H W; van Rooyen, J M; Schutte, R; Fourie, C M T; Malan, N T; Seedat, Y K

    2011-07-01

    The renin-angiotensin-aldosterone system can be activated by sympathetic nervous input and is thought to have an important role in the prevalence of hypertension and cardiovascular risk in black Africans. We examined (1) the association between plasma renin responses to mental stress and a marker of sub-clinical atherosclerosis; and (2) associations between resting renin and 24-h ambulatory blood pressure. Participants were 143 urbanized black African men and women (43.1 ± 7.7 years) drawn from a study of Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA). After an overnight fast, participants completed the Stroop mental stress task. Blood samples were drawn during baseline and 10 min after the task to assess the concentration of active renin in plasma. Blood pressure assessments included continuous Finometer measures during the stress testing and 24-h ambulatory monitoring. Carotid intima-media thickness (CIMT) was measured using high-resolution ultrasound. Approximately 50% of the sample responded to the task with an increase in renin concentration. Multiple linear regression analysis revealed an association between the renin stress response and CIMT (β = 0.024, 95% confidence interval, 0.004-0.043), after adjustment for conventional risk factors, blood pressure stress responses and basal levels of renin activity (R(2) for model = 0.37). In addition, resting renin was inversely associated with ambulatory blood pressure. In summary, heightened release of renin during a laboratory mental stressor was associated with a marker of sub-clinical atherosclerosis; thus, it may be a potential mechanism in explaining the increased burden of cardiovascular disease in urbanized black Africans.

  5. Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

    DEFF Research Database (Denmark)

    Rasch, Ruth; Jensen, B L; Nyengaard, Jens Randel

    1998-01-01

    In order to study the cellular mode of renin secretion, stereological methods were used to estimate number and volume of rat renin secretory granules during stimulation of the renin system. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min increased plasma renin concentration (PR...

  6. Effect of hydration on plasma vasopressin, renin, and aldosterone responses to head-up tilt

    Science.gov (United States)

    Harrison, M. H.; Geelen, G.; Keil, L. C.; Wade, C. A.; Hill, L. C.

    1986-01-01

    If plasma vasopressin (PVP), plasma renin (PRA), and plasma aldosterone (PA) responses to change in posture are mediated only by alterations in intrathoracic baroreceptor activity hydration status should have minimal influence on these responses. To test this hypothesis, six male subjects underwent 45 min of 70 deg head-up tilt (HUT) following 26 h dehydration, and again, 105 min later, following rehydration. Compared with preceding supine hydrated control values, PVP, PRA, and PA increased (p less than 0.001) during dehydrated HUT, but only PVP and PRA increased during rehydrated HUT (p less than 0.001). The dissociation during rehydrated HUT of PRA and PA may have been related more to the reduction (p less than 0.001) in plasma potassium concentration than to the accompanying decrease (p less than 0.001) in plasma osmolality and sodium concentration. Although increases in PVP and PRA during HUT were attenuated (p less than 0.01) following rehydration, this attenuation was associated with the absence of symptoms of overt hypotension following rehydration. However, since rehydration did not abolish the increases in PVP and PRA induced by HUT, it is concluded that the present observations support the concept of intrathoracic baroreceptor involvement in the regulation of vasopressin secretion and renin release.

  7. The patterns of peripheral plasma renin concentration in the early post-renal-transplant period.

    Science.gov (United States)

    Kornerup, H J

    1979-01-01

    Serial determinations of peripheral plasma renin concentration (PRC) were performed in 11 kidney transplant recipients during the early post-transplant period. In 5 recipients with late onset of graft function, PRC values were increased during the anuric phase and, subsequently, PRC values declined in every during restoration of graft function. In 4 recipients with an acute renal allograft reaction, PRC values were increased at the onset of the allograft reaction in 3 with hypertension whereas PRC values were normal in one normotensive recipient. Subsequently, PRC normalized in the hypertensives coincident with increasing body weights. In 2 recipients with an uncomplicated course and with a normal graft function immediately after transplantation and throughout the study period, PRC values were constantly normal. The results indicate that acute anuria in the early phase after kidney transplantation is associated with an increased release of renin. The results also suggest that an increased activity of the renin-angiotensin system may be counterbalanced by sodium and fluid retention in hypertension following an acute renal allograft reaction.

  8. CHBPR: ANGIOTENSIN II, INDEPENDENT OF PLASMA RENIN ACTIVITY, CONTRIBUTES TO THE HYPERTENSION OF AUTONOMIC FAILURE

    Science.gov (United States)

    Arnold, Amy C.; Okamoto, Luis E.; Gamboa, Alfredo; Shibao, Cyndya; Raj, Satish R.; Robertson, David; Biaggioni, Italo

    2013-01-01

    At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. While the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable suggesting renin-angiotensin pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that angiotensin II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating angiotensin II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/ml, n=11) compared to matched healthy controls (27±4 pg/ml, n=10; p=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/ml/hr, respectively; p=0.449). To determine the contribution of angiotensin II to supine hypertension in these patients, we administered the AT1 receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mmHg at 6 hours after administration (p<0.05), decreased nocturnal urinary sodium excretion (p=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of the captopril on supine blood pressure in a subset of these patients. These findings suggest that angiotensin II formation in autonomic failure is independent of plasma renin activity, and perhaps angiotensin converting enzyme. Furthermore, these studies suggest that elevations in angiotensin II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT1 receptor blockers for treatment of these patients. PMID:23266540

  9. Plasma catecholamines, renin and aldosterone during combined alpha- and beta- adrenoceptor blockade in patients with severe arterial hypertension.

    Science.gov (United States)

    Kornerup, H J; Pedersen, E B; Pedersen, A; Pedersen, G; Christensen, N J

    1980-01-01

    Arterial blood pressure and plasma catecholamines, renin activity and aldosterone concentration in 12 patients with severe essential hypertension were studied before and after combined alpha- and beta- adrenoceptor blockade induced by oral labetalol treatment for 2 months. Frusemide in a fixed dose was employed as a basic antihypertensive agent throughout the study. Blood pressure was adequately controlled in only 6 patients. Mean body weight increased by 1.8 kg and there was a rise in body weight which was inversely correlated with the fall in standing mean blood pressure. The mean plasma noradrenaline concentration decreased from 0.30 to 0.20 ng/ml, whereas plasma adrenaline did not change significantly. Plasma renin activity and aldosterone concentration varied greatly, but the mean values did not change significantly. Change in body weight was correlated inversely with changes in plasma noradrenaline and renin. The results suggest that labetalol, through its combined alpha- and beta- adrenoceptor blocking action, induces a rise in body weight, probably due to sodium and fluid retention, which partly counterbalances its anti-hypertensive effect and partly modifies both renin and sympathetic nervous activity.

  10. Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

    DEFF Research Database (Denmark)

    Egecioglu, E; Andersson, I J; Bollano, E

    2007-01-01

    .05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P pressure (BP, 110 +/- 4 vs. 147 +/- 3 mmHg, P ....05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice (P ... to acetylcholine (P causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size...

  11. Effect of topical propranolol gel on plasma renin, angiotensin II and vascular endothelial growth factor in superficial infantile hemangiomas.

    Science.gov (United States)

    Tang, Yu-juan; Zhang, Zai-zhong; Chen, Shao-quan; Chen, Shu-ming; Li, Cheng-jin; Chen, Jian-wei; Yuan, Bo; Xia, Yin; Wang, Lie

    2015-10-01

    The effect of topical propranolol gel on the levels of plasma renin, angiotensin II (ATII) and vascular endothelial growth factor (VEGF) in superficial infantile hemangiomas (IHs) was investigated. Thirty-three consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma renin, ATII and VEGF in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants of the same age from out-patient department. The clinical efficiency of topical propranolol gel at 1st, and 3rd month after application was 45%, and 82% respectively. The levels of plasma renin, ATII and VEGF in patients pre-treatment were higher than those in healthy infants (565.86 ± 49.66 vs. 18.19 ± 3.56, 3.20 ± 0.39 vs 0.30 ± 0.03, and 362.16 ± 27.29 vs. 85.63 ± 8.14, P 0.05). It was indicated that the increased renin, ATII and VEGF might play a role in the onset or development of IHs. Propranolol gel may suppress the proliferation of IHs by reducing VEGF.

  12. Influence of sedentary versus physically active conditions on regulation of plasma renin activity and vasopressin.

    Science.gov (United States)

    Mueller, Patrick J

    2008-09-01

    Physical inactivity is an independent risk factor for cardiovascular disease. Sedentary animals compared to physically active controls exhibit enhanced sympathoexcitatory responses, including arterial baroreflex-mediated sympathoexcitation. Hypotension-induced sympathoexcitation is also associated with the release of vasoactive hormones. We hypothesized that sedentary conditions may enhance release of the vasoactive hormones AVP and ANG II. To test this hypothesis, the humoral response to hypotension was examined in conscious rats after 9-12 wk of sedentary conditions or "normally active" conditions. Normally active conditions were produced by allowing rats access to running wheels in their home cages. Running distance peaked after 4 wk (4.5 +/- 0.7 km/day), and the total distance run after 9 wk was 174 +/- 23 km (n = 25). Similar levels of hypotension were induced in conscious sedentary or physically active animals with the arterial vasodilator, diazoxide (25 mg/kg iv). Control experiments used a saline injection of equivalent volume. Plasma samples were collected and assayed for plasma AVP concentration and plasma renin activity (PRA). Sedentary conditions significantly enhanced resting and hypotension-induced PRA relative to normal physical activity. In contrast, resting and hypotension-induced AVP levels were not statistically different between groups. These data suggest that baroreflex-mediated activation of the renin-angiotensin system, but not AVP secretion, is enhanced by sedentary conditions. We speculate that augmented activation of the renin-angiotensin system may be related to enhanced sympathetic outflow observed in sedentary animals and may contribute to increased risk of cardiovascular disease in the sedentary population.

  13. Effects of mildly increasing dialysis sodium removal on renin and sympathetic system in hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    Shen Yang; Sun Fang; Liu Jing; Ma Lijie; Huang Jing; Zhou Yilun; Liu Wenhu

    2014-01-01

    Background It has been argued that the benefits of reducing sodium loading may be offset by increased activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system.This study aimed to investigate the long-term effects of an increase in dialysis sodium removal on circulating RAAS and sympathetic system in hypertensive hemodialysis (HD) patients with "normal" post-HD volume status.Methods Thirty hypertensive HD patients were enrolled in this pilot trial.After one month period of dialysis with standard dialysate sodium of 138 mmol/L,the patients were followed up for a four months period with dialysate sodium set at 136 mmol/L,without changes in instructions regarding dietary sodium control.During the period of study,the dry weight was adjusted monthly under the guidance of bioimpedance spectroscopy to maintain post-HD volume status in a steady state; 44-hour ambulatory blood pressure,plasma renin,angiotensin Ⅱ (Ang Ⅱ),aldosterone,and norepinephrine (NE) were measured.Results After four months of HD with low dialysate sodium of 136 mmol/L,44-hour systolic and diastolic blood pressures (BPs) were significantly lower (-10 and-6 mmHg),in the absence of changes in antihypertensive medications.No significant changes were observed in plasma renin,Ang Ⅱ,aldosterone,and NE concentrations.The post-HD volume parameters were kept constant.Conclusion Mildly increasing dialysis sodium removal over 4 months can significantly improve BP control and does not activate circulating RAAS and sympathetic nervous system in hypertensive HD patients.

  14. End-organ damage in urbanized Africans with low plasma renin levels: the SABPA study.

    Science.gov (United States)

    van Rooyen, Johannes M; Schutte, Aletta E; Huisman, Hugo W; Schutte, Rudolph; Fourie, Carla M T; Malan, Nicolaas T; Malan, Leoné

    2014-01-01

    The purpose of this study was to evaluate whether active renin concentration is associated with markers of end-organ damage in urbanized Africans. This study forms part of the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. For this study, 81 men and 74 women were divided into low- and high-renin groups. Ambulatory blood pressure measurements were conducted. A resting 12-lead ECG was determined in order to determine the gender-specific Cornell voltage. Cardiovascular variables were continuously recorded with the Finometer. Carotid-dorsalis pedis pulse wave velocity was obtained with the Complior acquisition system. The carotid intima-media thickness (CIMT) was obtained with the SonoSite MicroMaxx. Blood samples were collected; serum and plasma were stored at -80 °C for analysis. Anthropometric measurements were taken using standard methods. A general health questionnaire was also completed. The urinary creatinine was determined with a calorimetric method and albumin with a turbidimetric method. The serum sodium and potassium were determined by making use of the Konelab TM 20i Sequential Multiple Analyzer Computer (SMAC). The concentration of active renin in the plasma was analyzed by making use of a high-sensitivity radio-immunometric assay. A negative association (r=-0.29, pplasma renin in the low-renin group (renin levels. It seems evident that low renin in black South Africans may result in sub-clinical renal damage and impaired vascular function in a group of urbanized black South Africans.

  15. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    Directory of Open Access Journals (Sweden)

    Indu Dhar

    Full Text Available The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs. Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs. HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH, proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  16. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    Science.gov (United States)

    Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

    2013-01-01

    The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

  17. Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H; Skøtt, O

    2000-01-01

    .6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), ED......(NaCl) increased by 3.6 mM, (P sodium excretion rate, or PRC. Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly....... There was a significant inverse relationship between superficial nephron ED(NaCl) and PRC. We conclude that ED(Na) decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium...

  18. Diagnostic evaluation of plasma aldosterone concentration to plasma renin activity ratio in primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    Huilan ZHANG; Daowen WANG

    2008-01-01

    Using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA ratio) as the screening test of choice for primary aldosteronism in hypertensive patients, we studied the clinical character-istics and the diagnostic value of PAC/PRA ratio in primary aldosteronism. The plasma aldosterone concen-tration (PAC) and plasma renin activity (PRA) levels were measured by radioimmunoassay in 902 hypertensive patients from out-patient clinics or hospitals. One hundred and twenty-six suspected primary aldosteronism patients whose PAC/PRA ratio was > 25 ng/dL/ng/mL/ hr had a lamellar computed tomography (CT) scan in the adrenal gland and follow-up visits. The proportion of primary aldosteronism in hypertensive patients was 14% (126/902). There were 54 patients with unilateral or bilateral hyperplasia and 25 patients with adenoma according to the CT scan. 39% (49/126) of the patients with primary aldosteronism had hypokalemia. Twenty-five patients received surgical treatment. The efficacy and cure rates were 100% (25/25) and 48% (12/25), respect-ively. The effective rate of aldactone and the single-drug cure rate were 89% (48/54) and 24% (13/54), respectively. Primary aldosteronism affects over 10% of hypertensive patients in China. The PAC/PRA ratio can be considered as a routine screening test in hypertensives, especially resistant hypertensive patients and a high PAC/PRA ratio is an invaluable index in primary aldosteronism diagnosis.

  19. Control of plasma renin activity in heat-stressed baboons on varied salt intake.

    Science.gov (United States)

    Proppe, D W

    1987-04-01

    The characteristics and control of the increase in plasma renin activity (PRA) during environmental heating (EH) were determined in 12 unanesthetized, chronically catheterized baboons. Each EH experiment consisted of a 1.5- to 4-h exposure to an ambient temperature of 39-44 degrees C until core temperature (Tc) reached 39.5-40.0 degrees C. These EH experiments were done on the baboon in an unblocked state and during beta-adrenergic receptor blockade produced by propranolol when on normal-to-high salt intake (NHSI) and on low-salt intake (LSI). PRA rose linearly with Tc during EH, but the increase in PRA was considerably larger when the baboon was on LSI. The PRA-Tc linear regression coefficients were 2.32 and 5.98 ng angiotensin I X ml-1 X h-1 X degrees C-1 in NHSI and LSI states, respectively. This rise in PRA during EH was completely eliminated during beta-blockade in both NHSI and LSI states. It is concluded that heat stress activates the sympathetic nervous system to stimulate beta-receptor-mediated renin secretion by the kidney, this activation is controlled primarily by internal thermoreceptors, and variations in salt intake alters only the magnitude of the increase in PRA during heat stress, not the mechanisms that produce it.

  20. Control of renin secretion from kidneys with renin cell hyperplasia.

    Science.gov (United States)

    Kurt, Birgül; Karger, Christian; Wagner, Charlotte; Kurtz, Armin

    2014-02-01

    In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic renin cells is yet unknown, we aimed to characterize the control of renin secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys from mice lacking aldosterone synthase (AS⁻/⁻ mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations. On the absolute level, renin secretion from isolated AS⁻/⁻ kidneys was more than 10-fold increased over wild-type kidneys. On the relative level, the stimulation of renin secretion by the β-adrenergic activator isoproterenol or by lowering of the concentration of extracellular Ca²⁺ was very similar between the two genotypes. In addition, the inhibitory effects of ANG II and of perfusion pressure were similar between the two genotypes. Deletion of connexin40 blunted the pressure dependency of renin secretion and the stimulatory effect of low extracellular Ca²⁺ on renin secretion in the same manner in kidneys of AS⁻/⁻ mice as in wild-type mice. Our findings suggest a high degree of functional similarity between renin cells originating during development and located at different positions in the adult kidney. They also suggest a high similarity in the expression of membrane proteins relevant for the control of renin secretion, such as β₁-adrenergic receptors, ANG II type 1 receptors, and connexin40.

  1. Thyroid hormones and renin secretion.

    Science.gov (United States)

    Ganong, W F

    Circulating angiotensin is produced by the action of renin from the kidneys on circulating angiotensinogen. There are other renin-angiotensin systems in various organs in the body, and recent observations raise the intriguing possibility that angiotensin II is produced by a totally intracellular pathway in the juxtaglomerular cells, the gonadotrops of the anterior pituitary, neurons, in the brain, salivary duct cells, and neuroblastoma cells. Circulating angiotensin II levels depend in large part on the plasma concentration of angiotensinogen, which is hormonally regulated, and on the rate of renin secretion. Renin secretion is regulated by an intrarenal baroreceptor mechanism, a macula densa mechanism, angiotensin II, vasopressin, and the sympathetic nervous system. The increase in renin secretion produced by sympathetic discharge is mediated for the most part by beta-adrenergic receptors, which are probably located on the juxtaglomerular cells. Hyperthyroidism would be expected to be associated with increased renin secretion in view of the increased beta-adrenergic activity in this condition, and hypothyroidism would be associated with decreased plasma renin activity due to decreased beta-adrenergic activity. Our recent research on serotonin-mediated increases in renin secretion that depend on the integrity of the dorsal raphe nucleus and the mediobasal hypothalamus has led us to investigate the effect of the pituitary on the renin response to p-chloroamphetamine. The response is potentiated immediately after hypophysectomy, but 22 days after the operation, it is abolished. This slowly developing decrease in responsiveness may be due to decreased thyroid function.

  2. Assays to measure nanomolar levels of the renin inhibitor CGP 38 560 in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cumin, F.; de Gasparo, M.; Wood, J.M.; Schnell, C.; Frueh, F.; Graf, P. (Ciba-Geigy Limited, Basel (Switzerland))

    1989-10-01

    A radioinhibitor binding assay and an enzyme inhibition assay have been developed to measure plasma levels of CGP 38 560, a potent human renin inhibitor. The detection limit of the assays was between 0.5 and 1 pmol/ml. There was a good correlation (r = 0.989) between the two assays for the measurement of human plasma spiked with CGP 38 560 in concentrations from 1.9 nM to 12 microM. Intra-assay variability was 6.1-17.3% and 4.4-27.2% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Interassay variability was 6.0-28.2% and 3.8-28.4% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Blood samples were collected during a pharmacological study performed in normotensive human volunteers on an unrestricted diet who were infused during a 30-minute period with CGP 38 560 A (50 micrograms/kg). Similar values for the concentrations of renin inhibitor in plasma were obtained with the radioinhibitor binding assay and the enzyme inhibitor assay, and there was a significant correlation between values obtained with the two different methodologies (r = 0.94). The plasma levels of renin inhibitor reached a maximum at the end of infusion and then decreased rapidly, indicating a short plasma half-life. The changes in biochemical parameters, plasma renin activity, and plasma concentration of active renin could be related to the concentrations of CGP 38 560 measured in the plasma.

  3. Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans. [Plasma Renin Activity and Plasma VasoPressin

    Science.gov (United States)

    Kravik, S. E.; Keil, L. C.; Geelen, G.; Wade, C. E.; Barnes, P. R.

    1986-01-01

    The effects of lower body and abdominal pressure, produced by antigravity suit inflation, on blood pressure, pulse rate, fluid and electrolyte shift, plasma vasopressin and plasma renin activity in humans in upright postures were studied. Five men and two women stood upright for 3 hr with the suit being either inflated or uninflated. In the control tests, the suit was inflated only during the latter part of the trials. Monitoring was carried out with a sphygnomanometer, with sensors for pulse rates, and using a photometer and osmometer to measure blood serum characteristics. The tests confirmed earlier findings that the anti-g suit eliminates increases in plasma renin activity. Also, the headward redistribution of blood obtained in the tests commends the anti-g suit as an alternative to water immersion or bed rest for initial weightlessness studies.

  4. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  5. Peptides and neurotransmitters that affect renin secretion

    Science.gov (United States)

    Ganong, W. F.; Porter, J. P.; Bahnson, T. D.; Said, S. I.

    1984-01-01

    Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the

  6. Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

    DEFF Research Database (Denmark)

    Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

    2016-01-01

    BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined...... blood pressure measurement, echocardiography, ECG, blood and urine analysis. RESULTS: Median ET-1 concentration was 1.29 (interquartile range [IQR], 0.97-1.82) pg/mL, median cortisol concentration 46.0 (IQR, 29.0-80.8) nmol/L, and median renin activity 0.73 (IQR, 0.48-1.10) ng/mL/h in all dogs. Overall...

  7. Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus : effects of RAAS stimulation

    NARCIS (Netherlands)

    Luik, PT; Kerstens, MN; Hoogenberg, K; Navis, GJ; Dullaart, RPF

    2003-01-01

    Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity a

  8. Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus : effects of RAAS stimulation

    NARCIS (Netherlands)

    Luik, PT; Kerstens, MN; Hoogenberg, K; Navis, GJ; Dullaart, RPF

    Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity

  9. Correlation of Salt Sensitivity, Plasma Renin Activity and Aldosterone in Hypertensive Patients

    Directory of Open Access Journals (Sweden)

    Tasic Nebojsa

    2017-09-01

    Full Text Available Plasma-renin values vary in normotensive and hypertensive populations. Some studies consider renin to be a key factor in the aetiology of hypertension, but other studies note that renin is an important factor in cardiovascular homeostasis and functions more as a growth factor than as a pressor hormone. The aim of this study was to assess the PRA and aldosterone values under different salt intake regimes in patients with essential hypertension. The study group consisted of 50 untreated patients (27 women and 23 men; average age 42±9,2 yrs.; average BMI 27,91±4,6 kg/m2 with essential hypertension. All patients were put on a high-sodium diet (200 mmol NaCl per day for one week after a week on a low-sodium diet (20 mmol NaCl per day. Sodium sensitivity (SS was defined as a 10-mmHg increase in the mean blood pressure at the end of the high- vs. the low-sodium diet. The SS group consisted of 26 patients, and the sodiuminsensitive group consisted of 24 patients. The PRA and aldosterone levels were determined in 12 patients. PRA values in the SS group during rest were significantly lower compared with the salt-resistant group during all regimes of salt intake (F=10,56, p=0,0012. Salt loading in SS patients causes a significant decrease in PRA (in rest and effort values in comparison to values during a low salt intake regime (rest: t=4,49, p<0,001; effort: t=3,45, p<0,01. The PRA values in the salt-resistant group did not vary significantly under the different salt intake regimes. The aldosterone values followed the pattern of the PRA values. It is necessary to distinguish investigations on salt intake effects based on incidence and value of blood pressure and investigations on salt restriction’s effects on of blood pressure levels (i.e., non-pharmacological hypertension therapy.

  10. Body fluids, circadian blood pressure and plasma renin during growth hormone administration: a placebo-controlled study with two growth hormone doses in healthy adults

    DEFF Research Database (Denmark)

    Møller, Jens; Jørgensen, Jens Otto Lunde; Frandsen, Erik

    1995-01-01

    Abstract Side effects that can be related to fluid retention are common during the initial phases of growth hormone (GH) administration. The aim of this study was to examine the changes in body fluid compartments, diurnal blood pressure and plasma renin concentration during GH administration...... of treatment a significant increase in renin (p = 0.03) was observed. Mean diurnal blood pressure levels remained unchanged, whereas mean diurnal heart rate (min-1) increased significantly (placebo, 75 +/- 3.6; 3 IU m-2, 79 +/- 3.2; 6 IU m-2, 79 +/- 3.7; p

  11. Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension.

    Science.gov (United States)

    Pedersen, O L; Mikkelsen, E; Christensen, N J; Kornerup, H J; Pedersen, E B

    1979-05-21

    Acute sublingual administration of nifedipine 10--20 mg to 13 hypertensive patients caused a rapid decrease in blood pressure (BP) and a concomitant increase in heart rate (HR), plasma noradrenaline (NA) and plasma renin activity (PRA); there was no significant change in plasma adrenaline (A) or aldosterone (ALDO). Basal PRA was the major determinant of the rise in PRA, as a close correlation was present between the basal value and the increase caused by nifedipine (r = 0.92), p less than 0.001). The rise in PRA was also correlated with the plasma concentration of nifedipine after 60 min (r = 0.80, p less than 0.01), but it was not correlated with the decrease in BP, the rise in HR or the increase in NA. Nifedipine 30--60 mg daily for 6 weeks caused a reduction in mean BP from 133 to 113 mmHg (p less than 0.001). Body weight and serum potassium decreased but no consistent change was noted in NA, PRA, ALDO or 24 h-excretion of catecholamines. A significant correlation was present between the change in NA and that in PRA (r = 0.74, p less than 0.01). The alterations in the various parameters in the acute and chronic studies were not correlated. The findings indicate that different regulatory mechanisms are activated during acute and chronic administration of nifedipine. It is suggested that an initial rise in sympathetic activity gradually decreases during prolonged therapy, but it still remains a determinant of PRA.

  12. Parathyroid hormone-related protein stimulates plasma renin activity via its anorexic effects on sodium chloride intake.

    Science.gov (United States)

    Atchison, Douglas K; Westrick, Elizabeth; Szandzik, David L; Gordish, Kevin L; Beierwaltes, William H

    2012-08-15

    Parathyroid hormone-related protein (PTHrP) increases renin release from isolated perfused kidneys and may act as an autacoid regulator of renin secretion, but its effects on renin in vivo are unknown. In vivo, PTHrP causes hypercalcemia and anorexia, which may affect renin. We hypothesized that chronically elevated PTHrP would increase plasma renin activity (PRA) indirectly via its anorexic effects, reducing sodium chloride (NaCl) intake and causing NaCl restriction. We infused male Sprague-Dawley rats with the vehicle (control) or 125 μg PTHrP/day (PTHrP) via subcutaneous osmotic minipumps for 5 days. To replenish NaCl consumption, a third group of PTHrP-infused rats received 0.3% NaCl (PTHrP + NaCl) in their drinking water. PTHrP increased PRA from a median control value of 3.68 to 18.4 ng Ang I·ml(-1)·h(-1) (P PTHrP + NaCl PRA value was normal (7.82 ng Ang I·ml(-1)·h(-1), P PTHrP). Plasma Ca(2+) (median control: 10.2 mg/dl; PTHrP: 13.7 mg/dl; PTHrP + NaCl: 14.1 mg/dl; P PTHrP (median control: 0.03 ng/ml; PTHrP: 0.12 ng/ml; PTHrP + NaCl: 0.15 ng/ml; P PTHrP- and PTHrP + NaCl-treated rats. Body weights and caloric consumption were lower in PTHrP- and PTHrP + NaCl-treated rats. NaCl consumption was lower in PTHrP-treated rats (mean Na(+): 28.5 ± 4.1 mg/day; mean Cl(-): 47.8 mg/day) compared with controls (Na(+): 67.3 ± 2.7 mg/day; Cl(-): 112.8 ± 4.6 mg/day; P PTHrP + NaCl group; 0.3% NaCl in the drinking water had no effect on PRA in normal rats. Thus, our data support the hypothesis that PTHrP increases PRA via its anorexic effects, reducing NaCl intake and causing NaCl restriction.

  13. Effects of exercise on plasma renin, aldosterone and catecholamines before and after surgery for aortic coarctation.

    Science.gov (United States)

    Sehested, J; Kornerup, H J; Pedersen, E B; Christensen, N J

    1983-01-01

    The pre- and postoperative values of blood pressure, pulse rate, plasma renin activity, plasma aldosterone concentration and circulating catecholamines were studied in a group of 12 patients with uncomplicated aortic coarctation before and after exercise. Mean age of patients studied was 21.5 years. Postoperative studies were carried out on average 204 days after surgery. Following operation, both resting and exercising upper extremity pressures decreased. Six out of the 11 patients still had an abnormally high exercising blood pressure when compared with a normal control group of six persons. Postoperative pulse rates during exercise were significantly higher than pre-operatively (P less than 0.01). No statistically significant differences between pre- and postoperative values, and between patients and normal controls were found in the hormonal studies. This study suggests that the renin-aldosterone-system does not have a major role in the maintenance of the hypertension associated with coarctation of the aorta.

  14. Implications of Plasma Renin Activity and Plasma Aldosterone Concentration in Critically Ill Patients with Septic Shock

    Directory of Open Access Journals (Sweden)

    Kyung Soo Chung

    2017-05-01

    Full Text Available Background The renin-angiotensin-aldosterone system is closely associated with volume status and vascular tone in septic shock. The present study aimed to assess whether plasma renin activity (PRA and plasma aldosterone concentration (PAC measurements compared with conventional severity indicators are associated with mortality in patients with septic shock. Methods We evaluated 105 patients who were admitted for septic shock. Plasma levels of the biomarkers PRA and PAC, the PAC/PRA ratio, C-reactive protein (CRP level, and cortisol level on days 1, 3, and 7 were serially measured. During the intensive care unit stay, relevant clinical information and laboratory results were recorded. Results Patients were divided into two groups according to 28-day mortality: survivors (n = 59 and non-survivors (n = 46. The survivor group showed lower PRA, PAC, Acute Physiologic and Chronic Health Evaluation (APACHE II score, and Sequential Organ Failure Assessment (SOFA score than did the non-survivor group (all P < 0.05. The SOFA score was positively correlated with PRA (r = 0.373, P < 0.001 and PAC (r = 0.316, P = 0.001. According to receiver operating characteristic analysis, the areas under the curve of PRA and PAC to predict 28-day mortality were 0.69 (95% confidence interval [CI], 0.58 to 0.79; P = 0.001 and 0.67 (95% CI, 0.56 to 0.77; P = 0.003, respectively, similar to the APACHE II scores and SOFA scores. In particular, the group with PRA value ≥3.5 ng ml-1 h-1 on day 1 showed significantly greater mortality than did the group with PRA value <3.5 ng ml-1 h-1 (log-rank test, P < 0.001. According to multivariate analysis, SOFA score (hazard ratio, 1.11; 95% CI, 1.01 to 1.22, PRA value ≥3.5 ng ml-1 h-1 (hazard ratio, 3.25; 95% CI, 1.60 to 6.60, previous history of cancer (hazard ratio, 3.44; 95% CI, 1.72 to 6.90, and coronary arterial occlusive disease (hazard ratio, 2.99; 95% CI, 1.26 to 7.08 were predictors of 28-day mortality. Conclusions Elevated

  15. Influence of season on plasma antidiuretic hormone, angiotensin II, aldosterone and plasma renin activity in young volunteers.

    Science.gov (United States)

    Kanikowska, Dominika; Sugenoya, Junichi; Sato, Maki; Shimizu, Yuuki; Inukai, Yoko; Nishimura, Naoki; Iwase, Satoshi

    2010-05-01

    We investigated seasonal changes in hormonal and thermoregulatory responses. Eight volunteers were subjected to the experiment at four times of the year: around the vernal and autumnal equinoxes, and at the summer and winter solstices at latitude 35 degrees N. Plasma antidiuretic hormone (ADH), angiotensin II (ANG II), aldosterone (ALD) and plasma renin activity (PRA) were analyzed before and after water immersion. Seasonal changes in thermoregulatory responses were assessed by measuring core temperature and sweat rate during immersion of the leg in hot water (at 42 degrees C) for 30 min in a room maintained at 26 degrees C. The concentration of plasma ADH and ALD before water immersion was significantly higher in summer than in other seasons. The concentrations of ANG II and PRA did not show seasonal variations. Changes in tympanic temperature during water immersion showed significant differences between seasons, and were higher in winter than in other seasons. The sweat rate was significantly higher in summer than in other seasons. In summary, ADH and ALD concentrations displayed a seasonal rhythm with marked elevation in summer; this may be a compensative mechanism to prevent dehydration from increased sweat loss during summer due to heat acclimatization.

  16. Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity.

    Science.gov (United States)

    Oparil, S; Ehrlich, E N; Lindheimer, M D

    1975-08-01

    1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.

  17. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

    NARCIS (Netherlands)

    Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Genevieve; Wenzel, Ulrich

    2014-01-01

    Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is stil

  18. Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion.

    Science.gov (United States)

    Qi, Ying; Wang, Xiaojing; Rose, Kristie L; MacDonald, W Hayes; Zhang, Bing; Schey, Kevin L; Luther, James M

    2016-02-01

    Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry-based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112-122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112-122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.

  19. Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays.

    NARCIS (Netherlands)

    Perschel, F.H.; Schemer, R.; Seiler, L.; Reincke, M.; Deinum, J.; Maser-Gluth, C.; Mechelhoff, D.; Tauber, R.; Diederich, S.

    2004-01-01

    BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma ren

  20. Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

    Science.gov (United States)

    Giles, Thomas D; Bakris, George; Oparil, Suzanne; Weber, Michael A; Li, Huiling; Mallick, Madhuja; Bharucha, David B; Chen, ChunLin; Ferguson, William G

    2015-11-01

    After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.

  1. Plasma Renin Activity and Aldosterone: Correlations with Moderate Hypohydration

    Science.gov (United States)

    1989-12-01

    MATERIALS AND METHODS min walk, 10 min rest with uninterrupted monitoring of Sixteen young adult male test subjects were recruited core temperature...specific gravity (S.G., refractometry ) was tested post- lib, but information on hydration status (assessed during prandially to assure adequate hydration...hemoglobin was quantitated using the cyanmethemoglo- test subjects were assigned to one of four clothing and bin method . Changes in plasma volume

  2. Plasma and tissue levels of proangiotensin-12 and components of the renin-angiotensin system (RAS) following low- or high-salt feeding in rats.

    Science.gov (United States)

    Nagata, Sayaka; Kato, Johji; Kuwasako, Kenji; Kitamura, Kazuo

    2010-05-01

    The renin-angiotensin system (RAS) is an essential regulator of the blood pressure and body fluid balance, but the processing cascade or role of the tissue RAS remains obscure. Proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, is assumed to function as a factor of the tissue RAS. To investigate the tissue production of proang-12, we measured the circulating and tissue components of the RAS including proang-12 following low-, normal-, or high-salt feeding in rats. Twelve-week-old male Wistar rats were fed a low-salt 0.3% NaCl or high-salt 8% NaCl diet for 7 days and compared with those fed a normal-salt diet of 0.7% NaCl. Low-salt feeding elevated the plasma renin activity and aldosterone concentration, resulting in significant increases in Ang I and Ang II levels in the plasma or kidney tissue, as compared with the normal- or high-salt group. Despite the increases in plasma renin activity, Ang I, and Ang II, the proang-12 levels in plasma and various tissues including the kidneys, small intestine, cardiac ventricles, and brain remained unchanged following low-salt feeding. These results suggest that peptide levels of proang-12 in rat plasma and tissues are regulated in a manner independent of the circulating RAS.

  3. The role of plasma volume, plasma renin and the sympathetic nervous system in the posture-induced decline in renal lithium clearance in man.

    Science.gov (United States)

    Smith, D F; Shimizu, M

    1978-01-01

    Excretion of lithium in urine was studied in 2 healthy males while recumbent and while upright, either walking or standing quietly. An oral dose of 24.3 mmol of Lit was taken as three lithium carbonate tablets 13 h before clearance tests. Renal lithium clearance decreased and lithium fractional reabsorption increased while upright. Standing immersed to the neck in water, which prevents the fall in plasma volume upon changing posture from recumbent to upright, prevented the fall in renal lithium clearance as well as the rise in lithium fractional reabsorption while upright. Oral doses of guanethidine (total dose of 200 mg) or oxprenolol (total dose of 140 mg) taken to prevent high levels of sympathetic nervous system activity and plasma renin, respectively, failed to prevent the fall in renal lithium clearance or the rise in lithium fractional reabsorption upon changing posture from recumbent to upright. The findings indicate that the fall in renal lithium clearance and the rise in lithium fractional reabsorption upon changing posture from recumbent to upright is related to the fall in plasma volume but not to high levels of sympathetic nervous system activity or plasma renin activity.

  4. Body fluids, circadian blood pressure and plasma renin during growth hormone administration: a placebo-controlled study with two growth hormone doses in healthy adults

    DEFF Research Database (Denmark)

    Møller, Jens; Jørgensen, Jens Otto Lunde; Frandsen, Erik

    1995-01-01

    Abstract Side effects that can be related to fluid retention are common during the initial phases of growth hormone (GH) administration. The aim of this study was to examine the changes in body fluid compartments, diurnal blood pressure and plasma renin concentration during GH administration......, and extracellular volume (ECV) and plasma volume (PV) were isotopically determined at day 6. Blood samples were obtained regularly. Diurnal blood pressure was recorded and 24-h urinary samples were collected at days 0, 6 and 14. ECV (l) was increased by GH (placebo, 19.58 +/- 0.82; 3 IU m-2, 20.77 +/- 1.22; 6 IU m...... of treatment a significant increase in renin (p = 0.03) was observed. Mean diurnal blood pressure levels remained unchanged, whereas mean diurnal heart rate (min-1) increased significantly (placebo, 75 +/- 3.6; 3 IU m-2, 79 +/- 3.2; 6 IU m-2, 79 +/- 3.7; p

  5. Correlation of hyponatremia with plasma renin activity, antidiuretic hormone and brain natri- uretic peptide in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    富路

    2006-01-01

    Objective To observe the changes of plasma renin activity, antidiuretic hormone and brain natriuretic peptide in chronic heart failure (CHF) and their correlation with hyponatremia. Methods Plasma levels of PRA, ADH, and BNP were measured by radioimmunology in 76 CHF patients. Forty-one out of 76 CHF patients with hyponatremia and 35 CHF patients without hyponatremia

  6. Plasma renin, plasma aldosterone and exchangeable sodium in normotensive and hypertensive kidney transplant recipients with and without transplant renal artery stenosis.

    Science.gov (United States)

    Kornerup, H J; Pedersen, E B

    1977-01-01

    Blood pressure (BP), plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and exchangeable sodium (ES) were studied in 19 kidney recipients on different fixed levels of sodium intake after successful kidney transplantation. The following groups of kidney recipients were investigated: group 1: 7 normotensives, group 2:7 hypertensives without transplant renal artery stenosis (TRAS), group 3:5 hypertensives with angiographically verified TRAS. Hypertension in the recipients without TRAS (group 2) was characterized by a positive correlation between BP and ES and a normal response of PRC and PAC to a fixed low (10 mEQ/day) and high (150 mEq/day) sodium intake. In contrast, hypertension in the recipients with TRAS (group 3) was characterized by a normal or varyingly increased PRC on a liberal sodium intake and a reduced response of PRC to sodium restriction, whereas PAC did not differ from the other groups of recipients. In one recipient in group 3 who underwent surgical correction for TRAS, PRC and PAC decreased before operation during sodium restriction, but BP remained high until after operation, when it normalized simultaneously with a decrease in ES. The results indicate that sodium retention is involved in the pathogenesis of posttransplant hypertension and suggest that an increased activity of the renin--angiotensin system is counterbalanced by an accumulation of sodium in TRAS.

  7. Age dependence of the levels of plasma norepinephrine, aldosterone, renin activity and urinary vanillylmandelic acid in normal and essential hypertensives.

    Science.gov (United States)

    Abd-Allah, Nadia M; Hassan, Fayeza H; Esmat, Amr Y; Hammad, Somaya A

    2004-01-01

    In the present study the upper reference limits (URLs) for resting plasma norepinephrine, epinephrine, serum aldosterone, plasma renin activity, aldosterone/renin activity ratio, as well as urinary vanillylmandelic acid in healthy Egyptian normotensive subjects over a range of ages (5-60 yr) were established. There was a significant age effect on plasma norepinephrine, UVMA, serum aldosterone and PRA, whereas a single URL for plasma epinephrine level is satisfactory. In uncomplicated untreated essential hypertensive subjects (5-60 yr), the average prevalence of elevation in the plasma norepinephrine, epinephrine and urinary vanillylmandelic acid above their corresponding URLs was 85.10, 62.15 and 83.20%, respectively. This suggests that elevation in plasma catecholamine concentrations is more likely a common consequence than playing a possible role in the pathogenesis of hypertension, supported by insignificant correlation coefficients between the plasma catecholamine levels and resting systolic and diastolic blood pressure values (SBP & DBP) in all hypertensive age groups. Primary hyperaldosteronism was not detected among the normokalemic essential hypertensives at any age using aldosterone/plasma renin activity ratio as a primary screening method. In the present study, 7 statistically significant positive coefficient correlations are reported for SBP or DBP values with UVMA levels in hypertensive children and adolescents, serum aldosterone in old hypertensives, and PRA in adult hypertensives.

  8. The Effect of Drinking on Plasma Vasopressin and Renin in Dehydrated Human Subjects

    Science.gov (United States)

    Geelen, G.; Keil, L. C.; Kravik, S. E.; Wade, C. E.; Thrasher, T. N.; Barnes, P. R.; Pyka, G.; Nesvig, C.; Greenleaf, J. E.

    1996-01-01

    Oropharyngeal mechanisms activated by drinking have been shown to induce a rapid decline in plasma vasopressin which preceeds postabsorptive changes in plasma composition in the dehydrated dog. The present study was undertaken to determine what factor(s) inhibit(s) vasopressin secretion after rehydration in water deprived human subjects. Hematocrit (Hct) and hemoglobin (Hb) were determined on the day of the experiment, together with electrolytes and osmolalities which were measured on freshly separated serum. Plasma was immediately frozen and further analyzed by radioimmunoassay for renin activity (PRA), vasopressin (AVP), and aldosterone. The data were analyzed using an analysis of variance for repeated measurements and significant differences between the dehydrated control period and various time points after the start of rehydration were determined using a multiple-range test. began and reached water replete levels 15 minutes after drinking in the absence of any detectable decline in serum sodium or osmolality, we conclude that 427 oropharyngeal factors, alone or combined with gastric distension account for the extremely rapid inhibition of AVP secretion after drinking in the water-deprived human, as has been shown to be the case in dogs. Our findings are also in agreement wiht the recent demonstration that at the onset of drinking in the dehydrated monkey, there is an abrupt fall in plasma AVP concentration associated with a considerable decrease in the firing rate of the supraoptic neurosecretory neurons.

  9. Correlation between propranolol in plasma and urine, renin-aldosterone system and blood pressure in essential hypertension.

    Science.gov (United States)

    Pedersen, E B; Kornerup, H J; Pedersen, O L; Andreasen, F; Bjerregaard, P

    1981-01-01

    Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg x 4 (Group 1), 80 mg x 4 (group 2) and 160 mg x 4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA an PAC fell in all groups, and remained reduced during C and D Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin -aldosterone system was initially suppressed in all group, but for unknown reasons it increased towards the control level after seven to eleven

  10. Selective hypoaldosteronism due to combined defects of the conversion from inactive renin to active renin and the aldosterone biosynthesis from corticosterone.

    Science.gov (United States)

    Muto, S; Akai, Y; Ono, S; Kusano, E; Asano, Y

    2001-07-01

    A 24-year-old Japanese woman with IgA nephropathy exhibited a decreased serum aldosterone level with normal plasma renin activity after toxemia of pregnancy. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid functions. Levels of serum corticosterone and deoxycorticosterone were normal. Resting plasma renin activity was normal, and plasma levels of total and inactive renin were increased. Rapid ACTH administration failed to stimulate any secretion of aldosterone, whereas it adequately increased serum cortisol, deoxycorticosterone, and corticosterone concentrations. Responses of both plasma renin activity and serum aldosterone level to the furosemide-posture challenge were blunted. Angiotensin II also failed to stimulate any secretion of aldosterone despite a progressive rise in blood pressure and an appropriate increase in serum corticosterone. These results suggest that combined defects of the conversion from inactive renin to active renin and aldosterone biosynthesis are the causes of selective hypoaldosteronism in our patient.

  11. Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

    Directory of Open Access Journals (Sweden)

    Jonas Dahlberg

    Full Text Available OBJECTIVE: Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC, thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity. METHODS: 39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques. RESULTS: Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR (18.0, 7.5-20.0 mmHg vs 6.0, 0.0-10.0 mmHg, P = 0.007 and lower plasma renin concentration (P-renin (6.0, 2.0-9.5 mU/L vs 15.0, 9.0-24.0 mU/L, P = 0.005 as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0-18.0 mmHg vs 5.0, 0.0-10.0 mmHg, P = 0.07 and P-renin (9.0, 6.0-16.0 mU/L vs 15.0, 9.0-28.0 mU/L, P = 0.03. CONCLUSION: Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension.

  12. Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

    Science.gov (United States)

    Kitagawa, H; Kitoh, K; Inoue, H; Ohba, Y; Suzuki, F; Sasaki, Y

    2000-04-01

    Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

  13. Plasma renin activity: An early marker of progressive renal disease in posterior urethral valves

    Directory of Open Access Journals (Sweden)

    Minu Bajpai

    2013-01-01

    Full Text Available Introduction: A significant number of children with posterior urethral valves (PUV develop chronic renal failure (CRF due to activation of the renin angiotensin system (RAS. We investigated the role of plasma renin activity (PRA in these cases and sought to establish a relationship between the accepted criteria of renal damage and PRA. Aims and Objectives: The aim of this study is to establish the relationship between PRA and CRF. Materials and Methods: The records of 250 patients with PUV were reviewed. Multiple linear regression analysis was used to assess correlations between PRA, grade of reflux, presence of scars and raised creatinine and decrease in glomerular filtration rates (GFR. A P < 0.5 was considered as significant. Results: A total of 58 patients were included. Their mean age was 16 years, range 5.3-24.2 years, mean follow-up period was 12.6 ± 3.6 years. At diagnosis, 22/58 (38% patients were in CRF and 36/58 (62% patients had normal renal function (RF. The mean PRA after treatment was higher in those who developed CRF than in those with normal RF (12.6 ± 10.2 vs. 34.6 ± 14.2 ng/ml/24 h, P = 0.02. Mean GFR at 1 year of age were 48 ± 9.8 ml/min/1.73 m 2 and 86 ± 12.5 ml/min/1.73 m 2 respectively (P = 0.005. PRA correlated negatively with GFR, t = -2.816, Confidence Interval: P = 0. 007. In the temporal plot over a period of 14 years, a rise in PRA preceded the fall in GFR in patients who developed CRF. Conclusions: This study shows that RAS is activated earlier in kidneys susceptible to damage. PRA could be investigated as a marker for the early detection and prevention of ongoing renal damage.

  14. Effects of renin inhibition in systemic hypertension.

    Science.gov (United States)

    Anderson, P W; Do, Y S; Schambelan, M; Horton, R; Boger, R S; Luther, R R; Hsueh, W A

    1990-12-01

    The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.

  15. Chronic activation of plasma renin is log-linearly related to dietary sodium and eliminates natriuresis in response to a pulse change in total body sodium.

    Science.gov (United States)

    Kjolby, Mads; Bie, Peter

    2008-01-01

    Responses to acute sodium loading depend on the load and on the level of chronic sodium intake. To test the hypothesis that an acute step increase in total body sodium (TBS) elicits a natriuretic response, which is dependent on the chronic level of TBS, we measured the effects of a bolus of NaCl during different low-sodium diets spanning a 25-fold change in sodium intake on elements of the renin-angiotensin-aldosterone system (RAAS) and on natriuresis. To custom-made, low-sodium chow (0.003%), NaCl was added to provide four levels of intake, 0.03-0.75 mmol.kg(-1).day(-1) for 7 days. Acute NaCl administration increased PV (+6.3-8.9%) and plasma sodium concentration (~2%) and decreased plasma protein concentration (-6.4-8.1%). Plasma ANG II and aldosterone concentrations decreased transiently. Potassium excretion increased substantially. Sodium excretion, arterial blood pressure, glomerular filtration rate, urine flow, plasma potassium, and plasma renin activity did not change. The results indicate that sodium excretion is controlled by neurohumoral mechanisms that are quite resistant to acute changes in plasma volume and colloid osmotic pressure and are not down-regulated within 2 h. With previous data, we demonstrate that RAAS variables are log-linearly related to sodium intake over a >250-fold range in sodium intake, defining dietary sodium function lines that are simple measures of the sodium sensitivity of the RAAS. The dietary function line for plasma ANG II concentration increases from theoretical zero at a daily sodium intake of 17 mmol Na/kg (intercept) with a slope of 16 pM increase per decade of decrease in dietary sodium intake.

  16. A longitudinal study of arterial blood pressure in chronic haemodialysis patients with different levels of plasma renin concentration.

    Science.gov (United States)

    Kornerup, H J; Fredsted, B; Pedersen, R S

    1978-01-01

    The purpose of the study was to examine the value of regular measurements of plasma renin concentration (PRC) in selecting those chronic haemodialysis patients suitable for bilateral nephrectomy to prevent development of uncontrollable hypertension. Regular measurements of arterial blood pressure (BP) and PRC were performed during one year in 31 patients undergoing regular haemodialysis because of end-stage renal disease. Among 18 patients with PRC greater than or equal to 100 micro Goldblatt units per ml plasma (microGU/ml) systolic and/or diastolic hypertension persisted or developed in 12. In contrast, among 13 patients with PRC greater than 100microGU/ml, BP became normal in all but one, who had a slightly increased systolic BP. However, hypertension was mild and easily controlled by conventional therapy in all except one, who probably had an overlying volume-dependent hypertension. Therefore, bilateral nephrectomy was not necessary in any case. The results indicate that hypertension in the majority of chronic haemodialysis patients with high PRC can be adequately controlled without surgical intervention and that regular measurements of PRC have no practical value in forecasting the development of uncontrollable hypertension in chronic haemodialysis patients.

  17. Use of Plasma Renin Activity to Monitor Mineralocorticoid Treatment in Dogs with Primary Hypoadrenocorticism: Desoxycorticosterone Versus Fludrocortisone

    OpenAIRE

    Baumstark, M E; Nussberger, J.; Boretti, F S; Baumstark, M W; Riond, B.; Reusch, C.E.; Sieber‐Ruckstuhl, N.S.

    2014-01-01

    Background Measurement of plasma renin activity (PRA) is the gold standard for monitoring mineralocorticoid treatment in humans with primary hypoadrenocorticism (PH). Objectives To compare PRA in dogs with newly diagnosed PH, dogs with diseases mimicking PH, and healthy dogs, and evaluate measurement of PRA to monitor therapeutic effects in dogs with PH treated with different mineralocorticoids. Animals Eleven dogs with newly diagnosed PH (group 1), 10 dogs with diseases mimicking PH (group 2...

  18. Plasma Renin Activity Predicts Blood Pressure Responses to β-Blocker and Thiazide Diuretic as Monotherapy and Add-On Therapy for Hypertension

    Science.gov (United States)

    Turner, Stephen T.; Schwartz, Gary L.; Chapman, Arlene B.; Beitelshees, Amber L.; Gums, John G.; Cooper-DeHoff, Rhonda M.; Boerwinkle, Eric; Johnson, Julie A.; Bailey, Kent R.

    2010-01-01

    BACKGROUND Age and race categories or renin profiling have been recommended to predict blood pressure responses to monotherapy with a β-blocker or thiazide diuretic. Whether these or other characteristics predict blood pressure responses when the drugs are administered as add-on therapy is uncertain. METHODS We evaluated predictors of blood pressure response in 363 men and women ≤65 years of age with primary hypertension (152 blacks, 211 whites), 86 of whom (24%) were untreated and 277 of whom (76%) were withdrawn from previous antihypertensive drugs before randomization to either atenolol followed by addition of hydrochlorothiazide (N = 180) or hydrochlorothiazide followed by addition of atenolol (N = 183). Responses were determined by home blood pressure averages before and after each drug administration. Race, age, plasma renin activity, and other characteristics including pretreatment blood pressure levels were incorporated into linear regression models to quantify their contributions to prediction of blood pressure responses. RESULTS Plasma renin activity and pretreatment blood pressure level consistently contributed to prediction of systolic and diastolic responses to each drug administered as mono- and as add-on therapy. Higher plasma renin activity was consistently associated with greater blood pressure responses to atenolol and lesser responses to hydrochlorothiazide. The predictive effects of plasma renin activity were statistically independent of race, age, and other characteristics. CONCLUSIONS Plasma renin activity and pretreatment blood pressure level predict blood pressure responses to atenolol and hydrochlorothiazide administered as mono- and as add-on therapy in men and women ≤65 years of age. PMID:20725057

  19. On the Origin of Urinary Renin: A Translational Approach.

    Science.gov (United States)

    Roksnoer, Lodi C W; Heijnen, Bart F J; Nakano, Daisuke; Peti-Peterdi, Janos; Walsh, Stephen B; Garrelds, Ingrid M; van Gool, Jeanette M G; Zietse, Robert; Struijker-Boudier, Harry A J; Hoorn, Ewout J; Danser, A H Jan

    2016-05-01

    Urinary angiotensinogen excretion parallels albumin excretion, which is not the case for renin, while renin's precursor, prorenin, is undetectable in urine. We hypothesized that renin and prorenin, given their smaller size, are filtered through the glomerulus in larger amounts than albumin and angiotensinogen, and that differences in excretion rate are because of a difference in reabsorption in the proximal tubule. To address this, we determined the glomerular sieving coefficient of renin and prorenin and measured urinary renin/prorenin 1) after inducing prorenin in Cyp1a1-Ren2 rats and 2) in patients with Dent disease or Lowe syndrome, disorders characterized by defective proximal tubular reabsorption. Glomerular sieving coefficients followed molecular size (renin>prorenin>albumin). The induction of prorenin in rats resulted in a >300-fold increase in plasma prorenin and doubling of blood pressure but did not lead to the appearance of prorenin in urine. It did cause parallel rises in urinary renin and albumin, which losartan but not hydralazine prevented. Defective proximal tubular reabsorption increased urinary renin and albumin 20- to 40-fold, and allowed prorenin detection in urine, at ≈50% of its levels in plasma. Taken together, these data indicate that circulating renin and prorenin are filtered into urine in larger amounts than albumin. All 3 proteins are subsequently reabsorbed in the proximal tubule. For prorenin, such reabsorption is ≈100%. Minimal variation in tubular reabsorption (in the order of a few %) is sufficient to explain why urinary renin and albumin excretion do not correlate. Urinary renin does not reflect prorenin that is converted to renin in tubular fluid.

  20. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice.

    Science.gov (United States)

    Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Geneviève; Wenzel, Ulrich O

    2014-08-01

    Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is still unclear. To determine whether increased expression of PRR is sufficient to induce cardiac or renal injury, we generated a mouse that constitutively overexpresses PRR by knocking-in the Atp6ap2/PRR gene in the hprt locus under the control of a CMV immediate early enhancer/chicken beta-actin promoter. Mice were backcrossed in the C57Bl/6 and FVB/N strain and studied at the age of 12 months. In spite of a 25- to 80-fold renal and up to 400-fold cardiac increase in Atp6ap2/PRR expression, we found no differences in systolic blood pressure or albuminuria between wild-type and PRR overexpressing littermates. Histological examination did not show any renal or cardiac fibrosis in mutant mice. This was supported by real-time PCR analysis of inflammatory markers as well as of pro-fibrotic genes in the kidney and collagen in cardiac tissue. To determine whether the concomitant increase of renin would trigger fibrosis, we treated PRR overexpressing mice with the angiotensin receptor-1 blocker losartan over a period of 6 weeks. Renin expression increased eightfold in the kidney but no renal injury could be detected. In conclusion, our results suggest no major role for PRR in organ damage per se or related to its function as a receptor of renin.

  1. The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production.

    Science.gov (United States)

    Tinning, Anne R; Jensen, Boye L; Schweda, Frank; Machura, Katharina; Hansen, Pernille B L; Stubbe, Jane; Gramsbergen, Jan Bert; Madsen, Kirsten

    2014-12-01

    Both the processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin (AQP)1 directly contributes to the recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and AQP1(+/+) mice were fed a low-salt (LS) diet [0.004% (wt/wt) NaCl] for 7 days and given enalapril [angiotensin-converting enzyme inhibitor (ACEI), 0.1 mg/ml] in drinking water for 3 days. There were no differences in plasma renin concentration at baseline. After LS-ACEI, plasma renin concentrations increased markedly in both genotypes but was significantly lower in AQP1(-/-) mice compared with AQP1(+/+) mice. Tissue renin concentrations were higher in AQP1(-/-) mice, and renin mRNA levels were not different between genotypes. Mean arterial blood pressure was not different at baseline and during LS diet but decreased significantly in both genotypes after the addition of ACEI; the response was faster in AQP1(-/-) mice but then stabilized at a similar level. Renin release after 200 μl blood withdrawal was not different. Isoprenaline-stimulated renin release from isolated perfused kidneys did not differ between genotypes. Cortical tissue norepinephrine concentrations were lower after LS-ACEI compared with baseline with no difference between genotypes. Plasma nitrite/nitrate concentrations were unaffected by genotype and LS-ACEI. In AQP1(-/-) mice, the number of afferent arterioles with recruitment was significantly lower compared with AQP1(+/+) mice after LS-ACEI. We conclude that AQP1 is not necessary for acutely stimulated renin secretion in vivo and from isolated perfused kidneys, whereas recruitment of renin-positive cells in response to chronic stimulation is attenuated or delayed in AQP1(-/-) mice.

  2. Renin, prorenin and the kidney: a new chapter in an old saga.

    Science.gov (United States)

    Ichihara, Atsuhiro; Sakoda, Mariyo; Kurauchi-Mito, Asako; Kaneshiro, Yuki; Itoh, Hiroshi

    2009-01-01

    The binding of prorenin to the (pro)renin receptor triggers 2 major pathways: a nonproteolytic conformational change in prorenin to its active form (angiotensin II-dependent pathway) and an intracellular pathway via the (pro)renin receptor itself (angiotensin II-independent pathway). In diabetic animals, an increased plasma prorenin level not only causes the generation of angiotensin II via the angiotensin II-dependent pathway, it also stimulates the transliteration receptors own intracellular signaling pathway in a manner that is independent of the generated angiotensin II. Thus, the administration of a "handle" region peptide (HRP), which acts as a decoy peptide and competitively inhibits the binding of prorenin to the (pro)renin receptor, has a beneficial effect in the kidneys of diabetic animals with low plasma renin levels. However, the benefits of HRP are slightly reduced in animal models of essential hypertension with relatively high plasma renin levels, and these benefits disappear altogether in animal models of hypertension with extremely high plasma renin levels. Thus, in the kidneys of animal models of diabetes and/or hypertension, both renin and prorenin competitively bind to the (pro)renin receptor and contribute to the pathophysiology of nephropathy. Consequently, renin, prorenin and the (pro) renin receptor may be important therapeutic targets for the prevention and regression of nephropathy in patients with diabetes and/or hypertension.

  3. Multiple ascending dose study with the new renin inhibitor VTP-27999: nephrocentric consequences of too much renin inhibition.

    Science.gov (United States)

    Balcarek, Joanna; Sevá Pessôa, Bruno; Bryson, Catherine; Azizi, Michel; Ménard, Joël; Garrelds, Ingrid M; McGeehan, Gerard; Reeves, Richard A; Griffith, Sue G; Danser, A H Jan; Gregg, Richard

    2014-05-01

    This study compared the pharmacodynamic/pharmacokinetic profile of the new renin inhibitor VTP-27999 in salt-depleted healthy volunteers, administered once daily (75, 150, 300, and 600 mg) for 10 days, versus placebo and 300 mg aliskiren. VTP-27999 was well tolerated with no significant safety issues. It was rapidly absorbed, attaining maximum plasma concentrations at 1 to 4 hours after dosing, with a terminal half-life of 24 to 30 hours. Plasma renin activity remained suppressed during the 24-hour dosing interval at all doses. VTP-27999 administration resulted in a dose-dependent induction of renin, increasing the concentration of plasma renin maximally 350-fold. This induction was greater than with aliskiren, indicating greater intrarenal renin inhibition. VTP-27999 decreased plasma angiotensin II and aldosterone. At 24 hours and later time points after dosing on day 10 in the 600-mg group, angiotensin II and aldosterone levels were increased, and plasma renin activity was also increased at 48 and 72 hours, compared with baseline. VTP-27999 decreased urinary aldosterone excretion versus placebo on day 1. On day 10, urinary aldosterone excretion was higher in the 300- and 600-mg VTP-27999 dose groups compared with baseline. VTP-27999 decreased blood pressure to the same degree as aliskiren. In conclusion, excessive intrarenal renin inhibition, obtained at VTP-27999 doses of 300 mg and higher, is accompanied by plasma renin rises, that after stopping drug intake, exceed the capacity of extrarenal VTP-27999 to block fully the enzymatic reaction. This results in significant rises of angiotensin II and aldosterone. Therefore, renin inhibition has an upper limit.

  4. Kidney transplant artery stenosis. Interrelationship between blood pressure, kidney function, renin-aldosterone system and body sodium content.

    Science.gov (United States)

    Kornerup, H J; Pedersen, E B; Fjeldborg, O

    1977-01-01

    Among 9 hypertensive recipients with kidney transplant artery stenosis (KTAS) evidence of increased activity of the renin system was present in 3. Surgical repair of KTAS in 4 recipients resulted in an increase in renal plasma flow and glomerular filtration rate associated with a decrease in exchangeable sodium and blood pressure. Peripheral plasma renin and aldosterone values were normal before and after operation in all. It is suggested that sodium retention may counterbalance increased activity of the renin system in KTAS. Preoperative determinations of plasma renin do not predict the effect of surgical repair of KTAS on hypertension.

  5. Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

    NARCIS (Netherlands)

    Javadi, S; Mol, JA; Boer, P; Boer, WH; Runberk, A

    2003-01-01

    The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were si

  6. Ultradian oscillations in plasma renin activity: their relationships to meals and sleep stages.

    Science.gov (United States)

    Brandenberger, G; Follenius, M; Muzet, A; Ehrhart, J; Schieber, J P

    1985-08-01

    The 24-h pattern of PRA was studied in 6 supine normal subjects, and the relationship between sleep stages and PRA oscillations was analyzed using 18 nighttime profiles and the concomitant polygraphic recordings of sleep. Blood was collected at 10-min intervals. The slow trends obtained by adjusting a third degree polynomial to the 24-h data were not reproducible among individuals, and no circadian pattern was detected. Sustained oscillations in PRA occurred throughout the day. Spectral analysis revealed that PRA oscillated at a regular periodicity of about 100 min during the night. This periodicity was modified during the daytime by meal intake, which induced PRA peaks with large interindividual variations in size. A close relationship was found between the nocturnal PRA oscillations and the alternance of rapid eye movement (REM) sleep and non-REM sleep. Non-REM sleep invariably coincided with increasing or peaking PRA levels. REM sleep occurred as PRA was declining or at nadirs. More precisely, increases in PRA marked the transition from REM sleep to stage II, whereas stages III and IV usually occurred when PRA was highest. This relationship between the periodic nocturnal oscillations in PRA and the alternance of the REM-non-REM cycles may translate a similar oscillatory process in the central nervous system or may be linked to hemodynamic changes during sleep that might be partly controlled by the renin-angiotensin system.

  7. Acute lead exposure increases arterial pressure: role of the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Maylla Ronacher Simões

    Full Text Available BACKGROUND: Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were treated with lead acetate (i.v. bolus dose of 320 µg/Kg, and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na(+,K(+-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1 produced blood lead levels of 37±1.7 µg/dL, which is below the reference blood concentration (60 µg/dL; 2 increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg; 3 increased ACE activity (27% compared to Ct and Na(+,K(+-ATPase activity (125% compared to Ct; and 4 did not change the protein expression of the α1-subunit of Na(+,K(+-ATPase, AT(1 and AT(2. Pre-treatment with an AT(1 receptor blocker (losartan, 10 mg/Kg or an ACE inhibitor (enalapril, 5 mg/Kg blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg did not prevent lead's hypertensive effect. CONCLUSION: Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular disease.

  8. Renal renin secretion as regulator of body fluid homeostasis

    DEFF Research Database (Denmark)

    Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane;

    2013-01-01

    intake, but the specific pathways involved and the relations between them are not well defined. In animals, renin secretion is a log-linear function of sodium intake. Close associations exist between sodium intake, total body sodium, extracellular fluid volume, and blood volume. Plasma volume increases...... by about 1.5 mL/mmol increase in daily sodium intake. Several lines of evidence indicate that central blood volume may vary substantially without measurable changes in arterial blood pressure. At least five intertwining feedback loops of renin regulation are identifiable based on controlled variables......The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

  9. Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice.

    Science.gov (United States)

    Wu, Chia-Hua; Mohammadmoradi, Shayan; Thompson, Joel; Su, Wen; Gong, Ming; Nguyen, Genevieve; Yiannikouris, Frédérique

    2016-07-01

    Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low-fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation.

  10. Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients.

    Science.gov (United States)

    Cho, Jung Sun; Ihm, Sang Hyun; Jang, Sung-Won; Chung, Woo-Baek; Choi, Yun-Seok; Shin, Dong-Il; Seo, Suk Min; Park, Mahn-Won; Kim, Gee Hee; Her, Sung-ho; Kim, Chan Joon; Kim, Tae-Hoon; Kang, Min Kyu; Chang, Kiyuk; Park, Chan Seok

    2014-01-01

    Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin-angiotensin-aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31 mmHg; n = 66) and the non-MS group (≤31 mmHg; n = 195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0 ± 5.4 ng/dl versus 12.2 ± 8.7 ng/dl, p < 0.001; PRA: 1.7 ± 1.3 ng/ml/h versus 2.6 ± 3.6 ng/ml/h, p = 0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6 ± 4.4 mm Hg for the non-MS group and 18.9 ± 4.9 mmHg for the MS group; p < 0.001 for each). It is generally accepted that the sympathetic nervous system plays a major role in the regulation of BP variability. Therefore, further studies on sympathetic nervous system activation in hypertensives with extreme MS are needed. MS in enrolled patients who were at relatively low risk in this study may be less affected by the RAAS.

  11. Renin release

    DEFF Research Database (Denmark)

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;

    2007-01-01

    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located......, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin...

  12. Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups

    Science.gov (United States)

    Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

    2000-01-01

    The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

  13. cAMP target sequences enhCRE and CNRE sense low-salt intake to increase human renin gene expression in vivo.

    Science.gov (United States)

    Desch, Michael; Harlander, Sabine; Neubauer, Björn; Gerl, Melanie; Germain, Stephane; Castrop, Hayo; Todorov, Vladimir T

    2011-05-01

    This study aimed to assess the role of cAMP target sequences enhancer cAMP response element (enhCRE) and cAMP and overlapping negative response element (CNRE) in the control of human renin gene (REN) in vivo. enhCRE and CNRE were silenced by mutations in a 12.2-kb human renin promoter fused to LacZ reporter gene. This construct was used to generate transgenic mice (RENMut-LacZ). The expression of the transgene was correctly targeted to the juxtaglomerular portions of renal afferent arterioles which express endogenous mouse renin. Therefore, enhCRE and CNRE do not seem to be relevant for the control of the cell-specific expression of the human renin gene. The β-adrenoreceptor agonist isoproterenol (10 mg/kg/day, for 2 days) stimulated the endogenous renin, but not the LacZ mRNA expression. Treatment of RENMut-LacZ mice with the angiotensin converting enzyme inhibitor (enalapril 10 mg/kg/day, for 7 days) or their crossing to angiotensin receptor type 1a knockout mice led to increased renin and LacZ mRNA levels. Renin expression was upregulated by low-salt diet (0.03% NaCl, for 10 days) and downregulated by high-salt diet (4% NaCl, for 10 days). In contrast, low-salt diet did not influence, while high-salt diet inhibited the expression of LacZ. In summary, enhCRE and CNRE appear to be necessary for the transactivation of the human renin gene through β-adrenoreceptors and by low-salt diet. Our data also suggest that different intracellular mechanisms mediate the effect of low- and high-salt intake on renin expression in vivo.

  14. The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion.

    Science.gov (United States)

    Machura, Katharina; Iankilevitch, Elina; Neubauer, Björn; Theuring, Franz; Kurtz, Armin

    2013-03-01

    On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.

  15. Association of Aldosterone, Plasma Renin Activity (PRA and Superoxide Dismutase (SOD with Inflammation and Insulin Resistance in Adult Men with Central Obesity

    Directory of Open Access Journals (Sweden)

    Hera Yuliana Intantri

    2011-08-01

    Full Text Available BACKGROUND: Visceral Obesity is related with chronic low grade inflammation, and is the main component of metabolic syndrome (MetS. MetS is associated with increased cardiovascular disease (CVD. Furthermore, superoxide dismutase (SOD is correlated with insulin resistance. Several studies have reported a strong correlation between Renin Angiotensin Aldosterone System (RAAS and CVD, but the association of Aldosterone, Plasma Renin Activity (PRA and SOD with inflammation, insulin resistance and MetS have not been fully elucidated. The aim of this study was to investigate the correlation of Aldosterone, PRA, and SOD with inflammation (high sensitivity c-reactive protein/hsCRP and insulin resistance (homeostasis model assessment-insulin resistance/HOMA-IR in adult men with central obesity. METHODS: This was a cross-sectional study, which was carried out on 80 male subjects with central obesity who were divided into 2 groups: the group of subjects who had fulfilled the MetS criteria and the other group of subjects who did not. After an overnight fasting, blood pressure (BP was measured on all subjects and laboratory examinations were done for measurement of the concentration of fasting glucose, high density lipoprotein cholesterol (HDL-C, triglyceride, hsCRP, insulin, aldosterone, PRA, and SOD. RESULTS: We found aldosterone had positive correlation with PRA (r=0.389; p<0.001 and triglycerides (r=0.234; p=0.036. PRA had positive correlation with SOD (r=0.220; p=0.05 and HDL-C (r=0.273; p=0.014, but not with hsCRP (r=-0.044; p=0.696 and HOMA-IR (r=0.168 p=0.136. PRA correlated with HOMA-IR in MetS (r=0.471; p=0.01. Aldosterone and PRA were correlated with diastolic pressure in those with hypertension (r=0.680; p=0.003 and r=0.608; p=0.01. CONCLUSIONS: There is no direct correlation between aldosterone or SOD and Insulin resistance, and inflammation in men with central obesity. The correlation between PRA and MetS might be through insulin resistance

  16. Effects on plasma angiotensin-converting enzyme activity and circulating renin of lisinopril and enalapril alone and in combination with propranolol in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, EF; Bendtsen, F; Henriksen, Jens Henrik Sahl

    1999-01-01

    The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and enalapril, alone and in combination with propranolol were studied. In an open, randomised, cross-over design 12 healthy volunteers received...... orally enalapril 20 mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma angiotensin-converting enzyme activity and plasma renin activity were measured for 24 h after each treatment period. Lisinopril...... and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, Penzyme activity remained significantly suppressed only after lisinopril (-60%, P

  17. Effects on plasma angiotensin-converting enzyme activity and circulating renin of lisinopril and enalapril alone and in combination with propranolol in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, Erik Feldager; Bendtsen, Flemming; Henriksen, Jens Henrik

    1999-01-01

    The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and enalapril, alone and in combination with propranolol were studied. In an open, randomised, cross-over design 12 healthy volunteers received...... orally enalapril 20 mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma angiotensin-converting enzyme activity and plasma renin activity were measured for 24 h after each treatment period. Lisinopril...... and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, Penzyme activity remained significantly suppressed only after lisinopril (-60%, P

  18. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure : An open-label, blinded end point, randomized prospective trial (VitD-CHF trial)

    NARCIS (Netherlands)

    Schroten, Nicolas F; Ruifrok, Willem P T; Kleijn, Lennaert; Dokter, Martin M; Silljé, Herman H; Lambers Heerspink, Hiddo J; Bakker, Stephan J L; Kema, Ido; van Gilst, Wiek H; van Veldhuisen, Dirk J; Hillege, Hans L; de Boer, Rudolf A

    2013-01-01

    Background Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis. Vitamin D may inhibit renin transcription and lower PRA. We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF pa

  19. Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats

    Science.gov (United States)

    Golin, Raffaello M. A.; Gotoh, Eiji; Keil, Lanny C.; Shackelford, Roy L.; Ganong, William F.

    1989-01-01

    The congenital vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus is associated with elevated plasma renin activity at rest and supernormal responses to stimuli that increase renin secretion. The mechanism underlying this phenomenon was investigated by infusing homozygous and heterozygous Brattleboro rats with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. The resulting data indicate that increased renin secretion in homozygous rats results from increased sympathetic activity. Because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

  20. Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats

    Science.gov (United States)

    Golin, Raffaello M. A.; Gotoh, Eiji; Keil, Lanny C.; Shackelford, Roy L.; Ganong, William F.

    1989-01-01

    The congenital vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus is associated with elevated plasma renin activity at rest and supernormal responses to stimuli that increase renin secretion. The mechanism underlying this phenomenon was investigated by infusing homozygous and heterozygous Brattleboro rats with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. The resulting data indicate that increased renin secretion in homozygous rats results from increased sympathetic activity. Because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

  1. Natriuretic peptides buffer renin-dependent hypertension.

    Science.gov (United States)

    Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

    2014-06-15

    The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

  2. Design of potent substrate-analogue inhibitors of canine renin

    Science.gov (United States)

    Hui, K. Y.; Siragy, H. M.; Haber, E.

    1992-01-01

    Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.

  3. Stimulation of renin secretion by catecholamines is dependent on adenylyl cyclases 5 and 6.

    Science.gov (United States)

    Aldehni, Fadi; Tang, Tong; Madsen, Kirsten; Plattner, Michael; Schreiber, Andrea; Friis, Ulla G; Hammond, H Kirk; Han, Pyung Lim; Schweda, Frank

    2011-03-01

    The sympathetic nervous system stimulates renin release from juxtaglomerular cells via the β-adrenoreceptor-cAMP pathway. Recent in vitro studies have suggested that the calcium-inhibited adenylyl cyclases (ACs) 5 and 6 possess key roles in the control of renin exocytosis. To investigate the relative contribution of AC5 and AC6 to the regulation of renin release in vivo we performed experiments using AC5 and AC6 knockout mice. Male AC5(-/-) mice exhibited normal plasma renin concentrations, renal renin synthesis (mRNA and renin content), urinary volume, and systolic blood pressure. In male AC6(-/-) mice, plasma renin concentration (AC6(-/-): 732 ± 119; AC6 (+/+): 436 ± 78 ng of angiotensin I per hour*mL(-1); Prenin synthesis were stimulated associated with an increased excretion of dilute urine (1.55-fold; Pplasma renin concentration by a single injection of the β-adrenoreceptor agonist isoproterenol (10 mg/kg IP) was significantly attenuated in AC5(-/-) (male: -20%; female: -33%) compared with wild-type mice in vivo. The mitigation of the plasma renin concentration response to isoproterenol was even more pronounced in AC6(-/-) (male: -63%; female: -50% versus AC6(+/+)). Similarly, the effects of isoproterenol, prostaglandin E2, and pituitary adenylyl cyclase-activating polypeptide on renin release from isolated perfused kidneys were attenuated to a higher extent in AC6(-/-) (-51% to -98% versus AC6(+/+)) than in AC5(-/-) (-31% to 46% versus AC5(+/+)). In conclusion, both AC5 and AC6 are involved in the stimulation of renin secretion in vivo, and AC6 is the dominant isoforms in this process.

  4. Itraconazole, a P-glycoprotein and CYP3A4 inhibitor, markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren.

    Science.gov (United States)

    Tapaninen, Tuija; Backman, Janne T; Kurkinen, Kaisa J; Neuvonen, Pertti J; Niemi, Mikko

    2011-03-01

    In a randomized crossover study, 11 healthy volunteers took 100 mg (first dose 200 mg) of the antifungal drug itraconazole, a P-glycoprotein and CYP3A4 inhibitor, or placebo twice daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren, a renin inhibitor used in the treatment of hypertension. Itraconazole raised the peak plasma aliskiren concentration 5.8-fold (range, 1.1- to 24.3-fold; P plasma aliskiren concentration-time curve 6.5-fold (range, 2.6- to 20.5-fold; P Plasma renin activity 24 hours after aliskiren intake was 68% lower during the itraconazole phase than during the placebo phase (P = .011). In conclusion, itraconazole markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren. The interaction is probably mainly explained by inhibition of the P-glycoprotein-mediated efflux of aliskiren in the small intestine, with a minor contribution from inhibition of CYP3A4. Concomitant use of aliskiren and itraconazole is best avoided.

  5. Direct renin inhibitor aliskiren increases AQP2 expression in renal collecting ducts and improves urinary concentration defect in NDI

    Institute of Scientific and Technical Information of China (English)

    LIN Yu; ZHANG Tie-zheng; ZHENG Pei-li; LI Chun-ling; WANG Wei-dong

    2016-01-01

    AIM:The direct renin inhibitor aliskiren displays antihypertensive and antialbuminuric effects in humans and in animal models . Emerging evidence has shown that aliskiren localizes and persists in medullary collecting ducts even after treatment was discontinued . The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression and improves urinary concen -trating defect induced by lithium .METHODS:The mice were either fed with normal chow or LiCl diet (40 mmol/kg dry food per day for first 4 days and 20 mmol/kg dry food per day for last 3 days ) for seven days .Some mice were intraperitoneally injected aliskiren ( 50 mg/kg BW per day in saline ) .RESULTS:Mice injected aliskiren developed decreased urine output and increased urine osmolal -ity when compared with controls .Aliskiren significantly increased protein abundance of AQP 2 and phosphorylated-S256 AQP2 in the kidney inner medulla .Immunohistochemistry and immunofluoresence showed increased apical and intracellular labeling of AQP 2 and pS256-AQP2 in collecting duct principal cells of kidneys in mice treated with aliskiren .Aliskiren treatment prevented urinary concen-trating defect in lithium-treated mice , and improved the downregulation of AQP 2 and pS256-AQP2 protein abundance in inner medulla of the kidney .In primary cultured rat inner medulla collecting duct cells , aliskiren dramatically increased AQP 2 protein abundance which was significantly inhibited either by PKA inhibitor H 89 or by adenylyl cyclase inhibitor MDL 12330, indicating an involvement of the cAMP signalling pathway in mediating aliskiren-induced increased AQP 2 expression .CONCLUSION: The direct renin inhibitor aliskiren upregulates AQP 2 protein expression in inner medullary collecting duct principal cells and prevents lithium -induced nephro-genic diabetes insipidus ( NDI) likely via PKA-cAMP pathways .

  6. Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells

    DEFF Research Database (Denmark)

    Desch, Michael; Schreiber, Andrea; Schweda, Frank;

    2010-01-01

    We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)gamma stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPARgamma. The mouse re...

  7. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

    Science.gov (United States)

    Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

    2015-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

  8. Effect of amlodipine on renin secretion and renin gene expression in rats.

    OpenAIRE

    Schricker, K.; Hamann, M.; Macher, A.; Krämer, B. K.; Kaissling, B; Kurtz, A.

    1996-01-01

    1. This study was done to characterize the influence of calcium channel blockade on renin secretion and renin gene expression in normal rats and rats with renovascular hypertension. To this end we studied the effects of the 1,4-dihydropyridine derivative, amlodipine, on plasma renin activity and renal renin m-RNA levels in normal rats and rats with unilateral renal hypoperfusion induced by applying 0.2 mm left renal artery clips over four days. 2. In normotensive rats, amlodipine significantl...

  9. Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations.

    Science.gov (United States)

    Fowler, Jason D; Krueth, Stacy B; Bernlohr, David A; Katz, Stephen A

    2009-02-01

    The renin-angiotensin system (RAS) has been implicated in a variety of adipose tissue functions, including tissue growth, differentiation, metabolism, and inflammation. Although expression of all components necessary for a locally derived adipose tissue RAS has been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two RAS components, renin and angiotensinogen (AGT), to determine the influence of their plasma concentrations on adipose and cardiac tissue levels in both perfused (plasma removed) and nonperfused samples. Variation of plasma RAS components was accomplished by four treatment groups: normal, DOCA salt, bilateral nephrectomy, and losartan. Adipose and cardiac tissue AGT concentrations correlated positively with plasma values. Perfusion of adipose tissue decreased AGT concentrations by 11.1%, indicating that adipose tissue AGT was in equilibrium with plasma. Cardiac tissue renin levels positively correlated with plasma renin concentration for all treatments. In contrast, adipose tissue renin levels did not correlate with plasma renin, with the exception of extremely high plasma renin concentrations achieved in the losartan-treated group. These results suggest that adipose tissue may control its own local renin concentration independently of plasma renin as a potential mechanism for maintaining a functional local adipose RAS.

  10. Renin and angiotensin levels in children.

    OpenAIRE

    Broughton Pipkin, F; Smales, O R; O'Callaghan, M.

    1981-01-01

    Plasma renin activity, plasma renin concentration, and angiotensin II levels were measured in 63 normal children aged between 2 months and 12 years. The results showed that the high levels of renin and angiotensin II present in infancy remained above adult levels throughout the first decade of life but that there was a decline with age. Boys less than 8 years old had lower plasma renin activity and angiotensin II levels than girls of a similar age; this may be due to a relative substrate defi...

  11. Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

    DEFF Research Database (Denmark)

    Krum, Henry; Massie, Barry; Abraham, William T

    2011-01-01

    AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) ...

  12. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

    Science.gov (United States)

    Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

    2015-06-01

    Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness in preeclampsia involves constrictor AT2 receptors.

  13. Heterogeneity of renin substrate released from hepatocytes and in brain extracts

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, E.; Eggena, P.; Barrett, J.D.; Sambhi, M.P.

    1984-01-23

    Renin substrate was characterized in incubation medium of isolated hepatocytes, plasma, and brain extracts of the rat by isoelectric focusing and polyacrylamide gel electrophoresis. The isoelectric focusing (IEF) profile of renin substrate released into incubation medium of rat hepatocytes demonstrated two peaks with isoelectric points (pI) of 4.1 (minor peak) and 4.6 (major peak). Extracts of normal rat brain also showed two forms (pI 4.6 major form, and pI 5.1 minor form). In contrast, normal rat plasma contained a single broad peak of substrate with pI 4.5. Intraperitoneal injection of 17..beta.. estradiol (1 mg) or bilateral nephrectomy significantly elevated renin substrate levels in plasma and increased its release from hepatocytes, however, no change in the IEF and PAGE profiles was evident. Molecular weights of renin substrate were 60,000-65,000 from all preparations. The presence of distinct forms of brain renin substrate and the lack of an increase in brain renin substrate following nephrectomy or estrogen treatment suggest local synthesis and support the postulate of an independent renin-angiotensin system in the central nervous system.

  14. An automated assay for the clinical measurement of plasma renin activity by immuno-MALDI (iMALDI).

    Science.gov (United States)

    Popp, Robert; Malmström, David; Chambers, Andrew G; Lin, David; Camenzind, Alexander G; van der Gugten, J Grace; Holmes, Daniel T; Pugia, Michael; Jaremek, Marta; Cornett, Shannon; Suckau, Detlev; Borchers, Christoph H

    2015-06-01

    Plasma renin activity (PRA) is essential for the screening and diagnosis of primary aldosteronism (PA), a form of secondary hypertension, which affects approximately 100 million people worldwide. It is commonly determined by radioimmunoassay (RIA) and, more recently, by relatively low-throughput LC-MS/MS methods. In order to circumvent the negative aspects of RIAs (radioisotopes, cross-reactivity) and the low throughput of LC-MS based methods, we have developed a high-throughput immuno-MALDI (iMALDI)-based assay for PRA determination using an Agilent Bravo for automated liquid handling and a Bruker Microflex LRF instrument for MALDI analysis, with the goal of implementing the assay in clinical laboratories. The current assay allows PRA determination of 29 patient samples (192 immuno-captures), within ~6 to 7h, using a 3-hour Ang I generation period, at a 7.5-fold faster analysis time than LC-MS/MS. The assay is performed on 350μL of plasma, and has a linear range from 0.08 to 5.3ng/L/s in the reflector mode, and 0.04 to 5.3ng/L/s in the linear mode. The analytical precision is 2.0 to 9.7% CV in the reflector mode, and 1.5 to 14.3% CV in the linear mode. A method comparison to a clinically employed LC-MS/MS assay for PRA determination showed excellent correlation within the linear range, with an R(2) value of ≥0.98. This automated high throughput iMALDI platform has clinically suitable sensitivity, precision, linear range, and correlation with the standard method for PRA determination. Furthermore, the developed workflow based on the iMALDI technology can be used for the determination of other proteomic biomarkers. This article is part of a Special Issue entitled: Medical Proteomics.

  15. Chronic effects of lead on the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Vander, A.J.

    1988-06-01

    This paper reviews the chronic effects of lead exposure on the renin-angiotensin system in experimental animals and human beings. In rats, when lead exposure is begun several weeks after birth in doses that cause blood lead concentration (PbB) of 30 to 40 ..mu..g/L, the result is an increase in basal plasma renin activity (PRA) and renal renin concentration, with no change in the metabolic clearance of renin; this is presumptive evidence for increased renin secretion. PRA is also increased in 1-month-old animals whose exposure to lead (in doses that raise PbB to 9 ..mu..g/dL) was begun in utero. In contrast, older animals whose exposure was begun in utero manifest no change or a decrease in their PRA and renal renin concentration. Regardless of when the exposure is begun, lead can decrease the plasma concentration of angiotensin II at any given PRA, but the dose required for this effect is highly variable. The hypertension induced by lead exposure is associated with low PRA and a normal anigotensin II/PRA ratio. Chronic human exposure to lead also is associated with highly variable changes in PRA from study to study; it has been reported to be decreased under both basal and stimulated conditions, unchanged, or increased in a manner exponentially related to PbB. The human data are consistent with the tentative hypothesis that lead-exposed persons may have higher PRA than normal during the early periods of modest exposure but normal or depressed PRA following more chronic severe exposures. In a small preliminary study, blood lead concentration was found to be higher in high-renin hypertensive persons than in normotensive persons.

  16. Prostaglandins stimulate renin secretion and renin mRNA in mouse renal juxtaglomerular cells

    DEFF Research Database (Denmark)

    Jensen, B L; Schmid, C; Kurtz, A

    1996-01-01

    This study examined 1) effects of prostaglandins (PG) on renin secretion and renin gene expression from isolated juxtaglomerular granular cells and 2) expression of cyclooxygenases in juxtaglomerular structures. Incubation of granular cell cultures with PGE2, -I2, -F2 alpha, and thromboxane B2...... identified PGI2 and PGE2 as stimulators of renin secretion; the effects were dose and time dependent. PGE2 also increased renin mRNA accumulation time and dose dependent. PGE2 and PGI2 activated adenylate cyclase concentration dependent in granular cells. PGE2 stimulations of renin secretion and renin m...

  17. Activation of the succinate receptor GPR91 in macula densa cells causes renin release.

    Science.gov (United States)

    Vargas, Sarah Laurin; Toma, Ildikó; Kang, Jung Julie; Meer, Elliott James; Peti-Peterdi, János

    2009-05-01

    Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) are salt sensors and generate paracrine signals that control renal blood flow, glomerular filtration, and release of the prohypertensive hormone renin. We hypothesized that the recently identified succinate receptor GPR91 is present in MD cells and regulates renin release. Using immunohistochemistry, we identified GPR91 in the apical plasma membrane of MD cells. Treatment of MD cells with succinate activated mitogen-activated protein kinases (MAPKs; p38 and extracellular signal-regulated kinases 1/2) and cyclooxygenase 2 (COX-2) and induced the synthesis and release of prostaglandin E(2), a potent vasodilator and classic paracrine mediator of renin release. Using microperfused JGA and real-time confocal fluorescence imaging of quinacrine-labeled renin granules, we detected significant renin release in response to tubular succinate (EC(50) 350 microM). Genetic deletion of GPR91 (GPR91(-/-) mice) or pharmacologic inhibition of MAPK or COX-2 blocked succinate-induced renin release. Streptozotocin-induced diabetes caused GPR91-dependent upregulation of renal cortical phospho-p38, extracellular signal-regulated kinases 1/2, COX-2, and renin content. Salt depletion for 1 wk increased plasma renin activity seven-fold in wild-type mice but only 3.4-fold in GPR91(-/-) mice. In summary, MD cells can sense alterations in local tissue metabolism via accumulation of tubular succinate and GPR91 signaling, which involves the activation of MAPKs, COX-2, and the release of prostaglandin E(2). This mechanism may be integral in the regulation of renin release and activation of the renin-angiotensin system in health and disease.

  18. Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans;

    2009-01-01

    hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF...

  19. Active immunization against renin in normotensive marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Michel, J.B.; Guettier, C.; Philippe, M.; Galen, F.X.; Corvol, P.; Menard, J.

    1987-06-01

    Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutneous injections of 30 ..mu..g each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of /sup 125/I-labeled human renin at a dilution of greater than or equal to 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly. Plasma renin enzyme activity was undetectable in the animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterize by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney.

  20. The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction

    Directory of Open Access Journals (Sweden)

    Paolo Verdecchia

    2008-10-01

    Full Text Available Paolo Verdecchia1, Fabio Angeli1, Giovanni Mazzotta1, Giorgio Gentile2, Gianpaolo Reboldi21Department of Cardiology, Clinical Research Unit ‘Preventive Cardiology’, Hospital ‘Santa Maria della Misericordia’, and Fondazione Umbra Cuore e Ipertensione – AUCI Onlus, Perugia, Italy; 2Department of Internal Medicine University of Perugia, ItalyAbstract: An association has been shown between plasma renin activity (PRA and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS can be inhibited through inhibition of angiotensin I (Ang I generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a lowmolecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.Keywords: plasma renin activity, renin angiotensin system, aliskiren, angiotensinogen, renin, hypertension, heart failure, diabetes

  1. Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways.

    Science.gov (United States)

    West, Crystal A; Shaw, Stefan; Sasser, Jennifer M; Fekete, Andrea; Alexander, Tyler; Cunningham, Mark W; Masilamani, Shyama M E; Baylis, Chris

    2013-11-15

    We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution, and increased renal medullary phosphodiesterase 5A (PDE5A) protein. The present study examined the role of the renin-angiotensin-aldosterone system (RAAS) in this mechanism. Virgin females were treated for 14 days with NIF (10 mg·kg(-1)·day(-1) via diet), NIF with spironolactone [SPR; mineralocorticoid receptor (MR) blocker, 200-300 mg·kg(-1)·day(-1) via diet], NIF with losartan [LOS; angiotensin type 1 (AT1) receptor blocker, 20 mg·kg(-1)·day(-1) via diet], enalapril (ENAL; angiotensin-converting enzyme inhibitor, 62.5 mg/l via water), or vehicle (CON). Mean arterial pressure (MAP) was reduced 7.4 ± 0.5% with NIF, 6.33 ± 0.5% with NIF + SPR, 13.3 ± 0.9% with NIF + LOS, and 12.0 ± 0.4% with ENAL vs. baseline MAP. Compared with CON (3.6 ± 0.3%), plasma volume factored for body weight was increased by NIF (5.2 ± 0.4%) treatment but not by NIF + SPR (4.3 ± 0.3%), NIF + LOS (3.6 ± 0.1%), or ENAL (4.0 ± 0.3%). NIF increased PDE5A protein abundance in the renal inner medulla, and SPR did not prevent this increase (188 ± 16 and 204 ± 22% of CON, respectively). NIF increased the α-subunit of the epithelial sodium channel (α-ENaC) protein in renal outer (365 ± 44%) and inner (526 ± 83%) medulla, and SPR prevented these changes. There was no change in either PDE5A or α-ENaC abundance vs. CON in rats treated with NIF + LOS or ENAL. These data indicate that the PVE and renal medullary adaptations in response to chronic vasodilation result from RAAS signaling, with increases in PDE5A mediated through AT1 receptor and α-ENaC through the MR.

  2. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  3. Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

    Directory of Open Access Journals (Sweden)

    E.P. Velloso

    2007-04-01

    Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

  4. Effect of the Arg389Gly β₁-adrenoceptor polymorphism on plasma renin activity and heart rate, and the genotype-dependent response to metoprolol treatment.

    Science.gov (United States)

    Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen; Broedbaek, Kasper; Hjelvang, Brian R; Henriksen, Trine; Frandsen, Erik; Forman, Julie L; Torp-Pedersen, Christian; Køber, Lars; Poulsen, Henrik E

    2012-09-01

    1. A gene-drug interaction has been indicated between β₁-adrenoceptor-selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). In the present study, we investigated the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR), as well as genotype-dependent responses to metoprolol and exercise. 2. Twenty-nine healthy male subjects participated in two treatment periods (placebo and 200 mg/day metoprolol). A 15 min submaximal exercise test was performed after each treatment period and PRA and HR were measured before and after exercise. 3. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol (P = 0.020) treatment. After placebo, the exercise-induced increase in PRA was greater in Gly/Gly than Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. 4. Resting PRA was lower in Gly/Gly than Arg/Arg subjects and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Thus, Gly/Gly heart failure patients may require lower doses of metoprolol than other patients to block neurohumoral hyperactivity.

  5. Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats

    DEFF Research Database (Denmark)

    Stubbe, Jane; Jensen, Boye L; Bachmann, Sebastian;

    2003-01-01

    We asked whether cyclooxygenase (COX) activity controls the renin-angiotensin system in the postnatal period. During kidney development, renin peaked at postnatal days 0-1 at the mRNA, tissue protein [renal renin concentration (RRC)], and plasma renin concentration (PRC) levels and was widely...

  6. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

    Energy Technology Data Exchange (ETDEWEB)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K. (Department of Cardiology, Postgraduate Medical School, Warsaw (Poland))

    1991-06-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 {times} 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications.

  7. Aliskiren, the first direct renin inhibitor for treatment of hypertension: The path of its development

    Directory of Open Access Journals (Sweden)

    M Jadhav

    2012-01-01

    Full Text Available Standard treatments available today for treating hypertension is diuretics, β-blockers, angiotensin converting enzyme inhibitors (ACEs, angiotensin receptor blockers (ARBs, calcium channel blockers, a-blockers, vasodilators, and centrally acting drugs. It is difficult to achieve the optimized renin angiotensin aldosterone system suppression with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate the compensatory feedback mechanism that increases renin release and increase plasma renin activity. The first orally active direct renin inhibitors (DRIs were developed in 1980s, including enalkiren, remikiren, and zankiren. However, poor absorption from the gastrointestinal tract, less bioavailability (<2%, short half life, and low potency hindered the development of these compounds. Aliskiren is the first DRI for the treatment of hypertension. Aliskiren is designed through a combination of molecular modeling techniques and crystal structure elucidation. Aliskiren effectively reduces the blood pressure as a mono therapy as well in combination therapy.

  8. Increased plasma aldosterone during atrial fibrillation declines following cardioversion

    DEFF Research Database (Denmark)

    Soeby-Land, C; Dixen, U; Therkelsen, S K;

    2011-01-01

    The renin-angiotensin-aldosterone system (RAAS) may be activated during atrial fibrillation (AF); our aim was to evaluate the level of aldosterone in patients with either permanent AF, persistent AF scheduled for cardioversion or patients in sinus rhythm (SR). We hypothesized that an increased...... level of aldosterone is found in patients with AF, decreasing in patients with restored SR....

  9. Reference Values for Aldosterone-Renin Ratios in Normotensive Individuals and Effect of Changes in Dietary Sodium Consumption

    NARCIS (Netherlands)

    Kerstens, Michiel N.; Kobold, Anneke C. Muller; Volmer, Marcel; Koerts, Jan; Sluiter, Wim J.; Dullaart, Robin P. F.

    2011-01-01

    BACKGROUND: Determination of the aldosterone-to-renin ratio (ARR) in blood is the preferred screening test for primary aldosteronism. Renin can be measured as the plasma renin activity (PRA) or the plasma renin concentration (PRC). Consequently, the ARR can be measured either based on the PRA (ARR(p

  10. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators.

    Science.gov (United States)

    Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G

    2016-07-01

    Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage.

  11. The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

    DEFF Research Database (Denmark)

    Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

    2012-01-01

    A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype......(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P effect on PRA. The effect of metoprolol concentration...... on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than in Arg/Arg subjects, and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than...

  12. Neural mechanisms by which gravitational stimuli and stress affect the secretion of renin and other hormones

    Science.gov (United States)

    Ganong, William F.

    1987-01-01

    The present goal is to determine by the production of discrete lesions the parts of the hypothalamus and brainstem that are involved in serotonin-mediated increases in renin secretion. A variety of stimuli which act in different ways to increase renin stimuli were developed and standardized. The experiments with p-chloroamphetamine (PCA) demonstrated that there is a serotonergic pathway which projects from the dorsal raphe nuclei to the paraventricular nuclei and the vetromedial nuclei of the hypothalamus; that projection from paraventricular nuclei to the brainstem and spinal cord may be oxytocinergic; and that the pathway from the spinal cord to the renin secreting cells is sympathetic. The demonstration that paraventicular lesions lower circulating renin substrate is important because it raises the possibility that substrate secretion is under neural control, either via the pituitary or by direct neural pathways. The discovery that lesions of the ventromedial nuclei appear to abolish the increase in renin secretion produced by many different stimuli without affecting the concentration of renin substrate in the plasma makes the position of the hypothalamus in the regulation of fluid and electrolyte balance more prominent than previously suspected.

  13. Effect of Blockade of Nitric Oxide Synthesis on the Renin Secretory Response to Frusemide in Conscious Rabbits

    Science.gov (United States)

    Reid, Ian A.; Chou, Lance

    1995-01-01

    The enzyme nitric oxide synthase is present in the macula densa and may participate in the control of renin secretion by the adjacent juxtagiomerular cells. In the present study, we investigated the effect of inhibiting nitric oxide synthase on the renin secretory response to frusemide, which stimulates renin secretion by blocking Na(+)-K(+)-2Cl(-) co-transport in the macula densa. Injection of frusemide in 12 conscious rabbits elicited a transient increase in mean arterial pressure from 84 +/- 2 to 92 +/-3 mm Hg at 5 min (P less than 0.01) and a sustained increase in heart rate from 246 +/- 6 to 281 +/- 10 beats/min at 45 min (P less than 0.01). Plasma renin activity increased from 8.0 +/- 1.2 to 14.3 +/- 1.8, 12.4 +/- 1.6 and 11.6 +/- 1.5 pmol/2h ml at 15, 30 and 45min respectively (P less than 0.01). There were no changes in plasma sodium and potassium concentrations or osmoiality. Inhibition of nitric oxide synthase with N(sup G)-nitro-L- arginine methyl ester increased mean arterial pressure by 9 mm Hg, decreased heart rate and plasma renin activity, and markedly suppressed the renin response to frusemide (from 4.6 +/- 0.7 to 7.6 +/- 1.7, 4.7 +/- 1.0 and 4.6 +/- 0.7pmol/2h ml at 15, 30 and 45 min respectively). By contrast, infusion of an equipressor dose of phenylephrine did not suppress the renin response to frusemide. Histochemical studies with the NADPH diaphorase technique confirmed the presence of nitric oxide synthase in the macula densa, and suggested that enzyme activity is increased by treatment with frusemide. These results are consistent with a role for the L- arginine-nitric oxide pathway in the modulation of renin secretion by the macula densa.

  14. Adrenomedullin stimulates renin release and renin mRNA in mouse juxtaglomerular granular cells

    DEFF Research Database (Denmark)

    Jensen, B L; Krämer, B K; Kurtz, A

    1997-01-01

    The recently discovered peptide adrenomedullin (AM) alters blood pressure through effects on the resistance vessels. Moreover, AM modifies the secretion of corticotropin and aldosterone and could thereby indirectly influence blood pressure through the renin-angiotensin-aldosterone system. Although...... on juxtaglomerular cells, possibly through increases in cAMP. AM could act as an autocrine/paracrine stimulatory factor in the control of renin secretion and renin gene expression....

  15. Paradoxical sleep deprivation increases plasma endothelin levels

    Directory of Open Access Journals (Sweden)

    B.D. Palma

    2002-01-01

    Full Text Available The endothelins (ET-1, 2 and 3 constitute a family of 21 amino acid peptides with potent biological activities. ET-1 is one of the most potent endogenous vasoconstrictors so far identified and its increased concentration in plasma appears to be closely related to the pathogenesis of arterial hypertension as well as to obstructive sleep apnea (OSA. OSA patients exhibit repetitive episodes of apnea and hypopnea that result in hypoxia and consecutive arousals. These patients are chronically sleep deprived, which may aggravate the hypertensive features, since literature data show that sleep deprivation results in hypertension both in humans and in animals. Based on the reported relationship between ET-1, hypertension and sleep deprivation consequences, the purpose of the present study was to determine plasma ET concentrations in paradoxical sleep-deprived animals. Male Wistar rats, 3 to 4 months old (N = 10 per group, were deprived of sleep for 24 and 96 h by the platform technique and plasma ET-1/2 was measured by radioimmunoassay. Analysis of plasma revealed that 96 h of sleep deprivation induced a significant increase in ET-1/2 release (6.58 fmol/ml compared to control (5.07 fmol/ml. These data show that sleep deprivation altered plasma ET-1/2 concentrations, suggesting that such an increase may participate in the genesis of arterial hypertension and cardiorespiratory changes observed after sleep deprivation.

  16. Direct renin inhibition — a new way of targeting the renin system

    Directory of Open Access Journals (Sweden)

    Morris J Brown

    2006-06-01

    Full Text Available The renin system plays a key role in the pathology of hypertension and is influenced, both directly and indirectly, by most antihypertensive agents. The system is the target of several established classes of antihypertensive agents including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. Of currently available drugs, only the beta-blockers suppress renin secretion, but these also reduce heart rate and cardiac output. Calcium channel blockers and diuretics cause a modest activation of the renin system secondary to the fall in renal afferent arteriolar pressure and reduction in filtered sodium load. Aliskiren is the first orally available direct inhibitor that blocks the renin system at its rate limiting step and is shown to reduce angiotensin I and II and plasma renin activity.

  17. Increased plasma fructosamine concentrations in laminitic horses.

    Science.gov (United States)

    Knowles, E J; Withers, J M; Mair, T S

    2012-03-01

    The use of plasma fructosamine concentration ([fructosamine]) as a marker of abnormal glucose homeostasis in laminitic horses has not been investigated. Plasma fructosamine concentration may be higher amongst laminitic horses than normal horses; this might relate to underlying insulin resistance. 1) To compare [fructosamine] between laminitic and normal horses. 2) To investigate associations between [fructosamine] at presentation in laminitic horses with a) single sample markers of insulin resistance and b) outcome. Plasma fructosamine concentration, fasting serum insulin concentration (insulin) and fasting plasma glucose concentration (glucose) were measured in 30 horses that presented with laminitis. Clinical details and follow-up data were recorded. Plasma fructosamine concentration was also measured in 19 nonlaminitic control horses. Laminitic horses had significantly higher mean [fructosamine] than normal horses (P<0.001). Thirteen of 30 laminitic horses had fasting hyperinsulinaemia, 2/30 had fasting hyperglycaemia. Statistically significant univariable correlations were identified between [fructosamine] and [glucose], [insulin] and the proxies RISQI and MIRG. Trends for association between [fructosamine] and negative outcome did not reach statistical significance. Increased mean [fructosamine] in laminitic horses may represent abnormal glycaemic control and [fructosamine] may become a clinically useful marker. © 2011 EVJ Ltd.

  18. Effects of lead on the renin-angiotensin system. [Rabbits; rats

    Energy Technology Data Exchange (ETDEWEB)

    Keiser, J.A.

    1982-01-01

    The renin-angiotensin system was evaluated in both acute and chronic lead-exposed rabbits and in unanaesthetized chronic lead-exposed rats. In addition, the acute effects of lead on in vitro secretion of renin were evaluated using rabbit and renal cortical slices. The clearance of renin was measured in chronic lead-exposed rats. Basal PRAs were significantly elevated in lead-exposed rats; renal renin activities were also significantly higher. In contrast, renin clearances were not different in the two groups. These findings support the hypothesis that the increase in basal PRA seen in lead-exposed rats is due to increased renin secretion not decreased hepatic removal of renin. In conclusion, we found no evidence for decreased renin degradation in the chronic lead-exposed rabbit or rat; rather, changes in renin secretion appear to account for observed increases in PRA. In contrast, acute lead-exposure inhibits both renin secretion and degradation in the rabbit.

  19. Regulation of renin secretion by renal juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla G; Madsen, Kirsten; Stubbe, Jane

    2013-01-01

    of stimulation; fetal life and chronic stimulation by extracellular volume contraction is associated with recruitment of renin-producing cells. Upon stimulation of renin release, labeled renin granules "disappear;" the number of granules decrease; cell membrane surface area increases in single cells, and release...... is quantal. Together, this indicates exocytosis as the predominant mode of release. JG cells release few percent of total renin content by physiological stimulation, and recruitment of renin cells is preferred to recruitment of granules during prolonged stimulation. Several endocrine and paracrine agonists...

  20. Changes in the renin-angiotensin-aldosterone system in response to dietary salt intake in normal and hypertensive pregnancy. A randomized trial

    DEFF Research Database (Denmark)

    Nielsen, Lise Hald; Ovesen, Per; Hansen, Mie R

    2016-01-01

    It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or placebo...... of plasma renin and angiotensin II in response to changes in dietary salt intake compatible with a primary increase in renal sodium reabsorption in hypertensive pregnancies....

  1. Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

    DEFF Research Database (Denmark)

    Rasch, Ruth; Jensen, B L; Nyengaard, Jens Randel

    1998-01-01

    ) twofold, but did not significantly change the number of renin granules per arteriole or the renin-containing volume of the arteriole. Chronic stimulation was achieved by a combination of low-salt diet and inhibition of angiotensin-converting enzyme (ACE) for 14 days, and resulted in a 36-fold increase...

  2. Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

    Science.gov (United States)

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin, aldosterone, norepinephrine (NE) and epinephrine (E) were determined during pregnancy, 5 days, 3, and 6 months after delivery in preeclampsia, normotensive pregnant, and nonpregnant control subjects. The PGE2 was higher in normotensive pregnant control subjects than in nonpregnant subjects. In preeclampsia, PGE2 was reduced to nonpregnant level. PGF2 alpha was the same in preeclampsia and in normotensive pregnancy, but elevated when compared to the normotensive nonpregnant control group. Plasma concentrations of renin and aldosterone were increased during pregnancy, but considerably less in preeclampsia than during normotensive pregnancy. NE and E were the same as in nonpregnant subjects during both hypertensive and normotensive pregnancy. All parameters were normal 3 months after delivery. There were no correlations between PGE2, PGF2 alpha, plasma concentrations of renin, aldosterone, NE, or E and blood pressure level in third trimester either in preeclampsia or in normotensive pregnancy. PGE2 was positively correlated to plasma concentrations of renin. It is suggested that the lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion. It is hypothesized that preeclampsia is a state of prostaglandin deficiency. The changes in the renin-aldosterone system may be secondary to changes in prostaglandin concentration both in preeclampsia and normotensive pregnancy.

  3. 不同体位血浆肾素和醛固酮及其比值诊断原发性醛固酮增多症的价值%Value of plasma renin, aldosterone and aldosterone to renin ratio in different positions to diagnosing primary aldosteronism

    Institute of Scientific and Technical Information of China (English)

    张玉杰; 李南方; 张菊红; 姚晓光; 李变

    2013-01-01

    Objective To discuss the values of plasma renin activity,plasma aldosterone concentration and aldosterone to renin ratio (ARR) in three positions (upright,sitting and supine positions) to diagnosing primary aldosteronism.Methods A total of 108 patients were detected plasma renin activity and plasma aldosterone concentration in three positions by using radioimmunity assay,and received intravenous saline load test.The ROC curves of plasma renin activity,plasma aldosterone concentration and ARR were drawn respectively on the basis of the intravenous saline load test results as diagnostic standard for primary aldosteronism.Results The AUC values of plasma aldosterone concentration and ARR in supine position were the biggest,indicating a high diagnostic accuracy for primary aldosteronism.The optimum cut-off points of ARR and plasma aldosterone concentration in supine position were 118.3 hours and 53 ng/L,with the coincidences of 57.1 % and 41.1% with intravenous saline load test to diagnose primary aldosteronism.The sensitivity,specificity and Youden index of the combination of ARR ≥ 118.3 hours with plasma aldosterone concentration ≥53 ng/L in supine position were 47.6%,94.1% and 0.471,with the coincident rate of 85.7 %.Conclusion In the patients unable to undergo intravenous saline load test,ARR (≥118.3 hours) combined with plasma aldosterone concentration (≥ 53 ng/L in supine position could improve the diagnosis rate of primary aldosteronism.%目的 探讨立、坐、卧位血浆肾素、醛固酮及醛固酮/肾素比值(aldosterone to renin ratio,ARR)对原发性醛固酮增多症(primary aldosteronism,PA)的诊断价值.方法 采用放射免疫法检测108例高血压患者立、坐、卧位血浆肾素活性及醛固酮水平,并行静脉盐水负荷试验;以静脉盐水负荷试验为PA的诊断标准,分别绘制肾素、醛固酮及ARR的ROC曲线.结果 卧位醛固酮的AUC最大,卧位ARR的AUC最大,诊断PA的准确性较高;

  4. Inhibition of calcineurin phosphatase promotes exocytosis of renin from juxtaglomerular cells

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Friis, Ulla Glenert; Gooch, Jennifer L;

    2010-01-01

    To examine the role of the calcium/calmodulin-dependent phosphatase calcineurin in regulation of renin release, we assayed exocytosis using whole-cell patch clamp of single juxtaglomerular cells in culture. The calcineurin inhibitor, cyclosporine A (CsA), significantly increased juxtaglomerular......A, but not tacrolimus, significantly stimulated renin release from cultured juxtaglomerular cells. Juxtaglomerular cells expressed the calcineurin isoforms A-beta and A-gamma but not A-alpha. Plasma renin concentrations (PRCs) were not different in wild-type, calcineurin A-alpha, or A-beta knockout mice but increased...... cell membrane capacitance, an index of cell surface area and an established measure of exocytosis in single-cell assays. This effect was mimicked by intracellular delivery of a calcineurin inhibitory peptide, the calcium chelator ethylene glycol tetraacetic acid (EGTA), or the calmodulin inhibitor W-13...

  5. Effect on manganese exposure on blood prolactin and plasma renin activity%锰接触对血中催乳素和血浆肾素活性的影响

    Institute of Scientific and Technical Information of China (English)

    牛侨; 何淑嫦; 陈艺兰; 代伏英; 王建英; 李怀应

    2001-01-01

    采用放射免疫的方法测定锰作业工人血中催乳素和血浆肾素活性,以探讨锰对内分泌和循环系统的影响。结果表明:锰接触组的血中催乳素浓度、肾素活性均明显高于对照组,提示锰接触可能影响结节-漏斗部位的功能,锰还可通过肾素-血管紧张素-醛固酮系统影响循环系统功能。%In order to study the adverse effects of manganese onneuro-endocrine and cardiovascular system, radioimmunoassay(RIA) was used to test the blood prolactin concentration and plasma renin activity among manganese-exposed workers The result showed that the blood prolactin concentration and Plasma renin activity in manganese exposed workers were significantly higher than those of control group.It suggested that manganese exposure might affect the function at tubero-infundibular area and renin-angiotensin aldosterone system.

  6. Genome-Wide Meta-Analyses of Plasma Renin Activity and Concentration Reveal Association with the Kininogen 1 and Prekallikrein Genes

    NARCIS (Netherlands)

    Lieb, Wolfgang; Chen, Ming-Huei; Teumer, Alexander; de Boer, Rudolf A; Lin, Honghuang; Fox, Ervin R; Musani, Solomon K; Wilson, James G; Wang, Thomas J; Völzke, Henry; Petersen, Ann-Kristin; Meisinger, Christine; Nauck, Matthias; Schlesinger, Sabrina; Li, Yong; Ménard, Joël; Hercberg, Serge; Wichmann, H-Erich; Völker, Uwe; Rawal, Rajesh; Bidlingmaier, Martin; Hannemann, Anke; Dörr, Marcus; Rettig, Rainer; van Gilst, Wiek H; van Veldhuisen, Dirk J; Bakker, Stephan J L; Navis, Gerjan; Wallaschofski, Henri; Meneton, Pierre; van der Harst, Pim; Reincke, Martin; Vasan, Ramachandran S

    2015-01-01

    BACKGROUND: -The renin-angiotensin-aldosterone-system (RAAS) is critical for regulation of blood pressure and fluid balance and influences cardiovascular remodeling. Dysregulation of the RAAS contributes to cardiovascular and renal morbidity. The genetic architecture of circulating RAAS components i

  7. Kallikrein and Renin in the Membrane Fractions of the Rat Kidney.

    Science.gov (United States)

    1980-05-23

    and Renin _____ ___ i.;? - 2 SUMMARY Plasma membrane (P-H) and endoplasmic reticulum (ER) enriched fractions were isolated from the homogenized rat...The inhibitor of proteases, p-methylsulfonylfluoride inhibited 77-80% all kallikrein preparations at 3 w*1 concentration . Activation of renin Renin ...fold although only at a concentration 5-10 times higher than used with kallikrein. The relative rate of activation of renin in the ER fraction was

  8. Intrarenal activation of renin angiotensin system in the development of cyclosporine A induced chronic nephrotoxicity

    Institute of Scientific and Technical Information of China (English)

    SHANG Ming-hua; YUAN Wei-jie; ZHANG Shujian; FAN Yu; ZHANG Zheng

    2008-01-01

    Background The relationship between cyclosporine-induced chronic nephrotoxicity (CAN) and renin-angiotenein Ⅱ in humans is still contradictory. This study was conducted to detect the levels of renin and angiotensin Ⅱ (ANGII) both in renal tissue and plasma from kidney transplantation patients suffering from CAN.Methods Twenty-six patients with allograft biopsy-proven CsA-related chronic nephrotoxicity (CAN group) and chronic rejection (control group) were enrolled in this study. Renal tissues were subjected to immunohistochemical staining with renin and ANGII antibodies. Renin and ANGII plasma levels were measured when the biopsy was performed. The relationship between expression of renin or ANGII and clinicopathological manifestations were also investigated. The cyclosporine plasma level was obtained 2 hours after morning dose (C2). In vitro, human umbilical vein endothelial cells (HUVEC) and rat mesangial cells (MC) were incubated with different concentrations of CsA (0, 250, 500, 1000 μg/L) for 24 hours. Secretion and expression of renin and ANGII was measured by radioimmunoassay or immunohistochemical staining.Results Renal pathological scores for renin and ANGII expression were significantly higher in specimens of CAN than in controls (P<0.05). The plasma levels of renin, ANGII and C2 in the CAN group were higher than the control group, but no significant difference was found ((0.37±0.12) ng.ml-1·h-1 vs (0.20±0.10) ng.ml-1·h-1, P=0.076; (122.69±26.73) pg/ml vs(121.88±36.35) pg/ml, P=0.977; (719.04±55.89) ng/ml vs (658.80±90.78) ng/ml, P=0.196, respectively). In vitro, renin as well as ANGII expression increased significantly in both HUVEC and MC after the cells were incubated with CsA for 24 hours (P <0.05). CsA also stimulated the secretion of ANGII in HUVEC and MC in a dose-dependent manner.Conclusions Renal allograft biopsy is important to differentiate chronic CsA-related nephropathy from chronic rejection. The intrarenal renin angiotensin

  9. Effect of contrasted sodium diets on the pharmacokinetics and pharmacodynamic effects of renin-angiotensin system blockers.

    Science.gov (United States)

    Azizi, Michel; Blanchard, Anne; Charbit, Beny; Wuerzner, Grégoire; Peyrard, Séverine; Ezan, Eric; Funck-Brentano, Christian; Ménard, Joël

    2013-06-01

    Dietary sodium, the main determinant of the pharmacodynamic response to renin-angiotensin system blockade, influences the pharmacokinetics of various cardiovascular drugs. We compared the effect of contrasted sodium diets on the pharmacokinetics of single oral doses of 8 mg candesartan cilexetil, 160 mg valsartan, 10 mg ramipril, and 50 mg atenolol administered to 64 (16 per group) normotensive male subjects randomly assigned to sodium depletion (SD) or sodium repletion (SR) in a crossover study. Pharmacodynamic response was assessed as the increase in plasma renin concentration for renin-angiotensin system blockers and electrocardiographic changes in PR interval duration for atenolol. The area under the curve (AUC) for plasma candesartan and atenolol concentrations was significantly lower for SR than for SD (respective ratios of AUC0-∞: 0.74; [90% CI, 0.66-0.82] and 0.69 [90% CI, 0.54-0.88], respectively), indicating a lack of bioequivalence between SR and SD. SR did not affect the pharmacokinetics of valsartan or ramipril. The increase in plasma renin concentration with the 3 renin-angiotensin system blockers was 10 times lower during the SR than the SD period. In the multiple regression analysis, the AUC0-24 of plasma drug concentration explained plasma renin concentration for candesartan (P=0.8882/P=0.0368) during the SR and SD periods, respectively. The atenolol-induced lengthening of PR interval was fully reversed by SR. Thus, sodium balance modulates the pharmacokinetics of candesartan cilexetil and atenolol, with measurable effects on the selected pharmacodynamic end points.

  10. Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

    Science.gov (United States)

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-10-01

    We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

  11. One-hour upright posture is an ideal position for serum aldosterone concentration and plasma renin activity measuring on primary aldosteronism screening.

    Science.gov (United States)

    Yin, G; Zhang, S; Yan, L; Wu, M; Xu, M; Li, F; Cheng, H

    2012-07-01

    The serum aldosterone concentration (SAC) to plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the variation of ARR and compare the screening efficiency of it under different postures.37 patients with PA and 92 patients with EH were recruited in this study. Blood was sampled for measuring SAC and PRA under conditions of overnight recumbency, keeping upright posture for 1 h, 2 h and 4 h. The variation and screening efficiency of ARR under these conditions were compared according to repeated measured ANOVA and ROC curve analysis.In the EH group, ARR measured under recumbency posture was higher than those measured under keeping upright posture for 1 h and 2 h. In the PA group, there is no statistical difference for ARR between any 2 postures. AUCs of ARR measured under 4 conditions were 0.976, 0.995, 0.988, and 0.974 respectively. Cutoff values were ranging from 24.75 ng/dl per ng/ml/h under keeping upright for 2 h to 69.19 ng/dl per ng/ml/h under overnight recumbercy. ARR measured under keeping upright posture for 1 h produced the best characteristic of screening efficiency.Keeping upright posture for 1 h was the ideal position for ARR measuring and using a cutoff value of 35.90 ng/dl per ng/ml/h will have a sensitivity and specificity of 100.00% and 92.30% respectively.

  12. A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice.

    Science.gov (United States)

    Tanimoto, Keiji; Kanafusa, Sumiyo; Ushiki, Aki; Matsuzaki, Hitomi; Ishida, Junji; Sugiyama, Fumihiro; Fukamizu, Akiyoshi

    2014-10-01

    Renin is predominantly expressed in juxtaglomerular cells in the kidney and regulates blood pressure homeostasis. To examine possible in vivo functions of a mouse distal enhancer (mdE), we generated transgenic mice (TgM) carrying either wild-type or mdE-deficient renin BACs (bacterial artificial chromosome), integrated at the identical chromosomal site. In the kidneys of the TgM, the mdE contributed 80% to basal renin promoter activity. To test for possible physiological roles for the mdE, renin BAC transgenes were used to rescue the hypotensive renin-null mice. Interestingly, renal renin expression in the Tg(BAC):renin-null compound mice was indistinguishable between the wild-type and mutant BAC carriers. Surprisingly, however, the plasma renin activity and angiotensin I concentration in the mdE compound mutant mice were significantly lower than the same parameters in the control mice, and the mutants were consistently hypotensive, demonstrating that blood pressure homeostasis is regulated through transcriptional cis elements controlling renin activity.

  13. (Pro)renin and (pro)renin receptor expression during kidney development in neonates.

    Science.gov (United States)

    Terada, Tomomasa; Urushihara, Maki; Saijo, Takahiko; Nakagawa, Ryuji; Kagami, Shoji

    2017-02-01

    Although a recent study demonstrated that the (pro)renin receptor ((P)RR) was highly expressed in the developing kidney during the mouse embryonic development, the mechanism by which (P)RR supports renal development in humans is not fully understood. In this study, we examined the plasma levels of (pro)renin and soluble (P)RR (s(P)RR) in cord blood and neonates as well as (P)RR expression in human kidney tissues. Samples were collected from 57 preterm and 67 full-term human neonates. (Pro)renin and s(P)RR levels were measured using enzyme-linked immunosorbent assays. Additionally, we performed an immunohistochemical (IHC) analysis of kidney tissues from neonates and minor glomerular abnormalities in order to assess (P)RR expression in the kidney. Plasma (pro)renin and s(P)RR levels in cord blood were significantly higher in preterm neonates than in full-term neonates. Four weeks after birth, these differences were no longer evident for either plasma (pro)renin or s(P)RR levels between the two groups. Importantly, plasma (pro)renin and s(P)RR levels in cord blood were inversely correlated with gestational age. Furthermore, IHC indicated that renal expression levels of (P)RR in neonates were stronger than those in minor glomerular abnormalities. (P)RR may play a pivotal role in prenatal renal development in humans. What is Known: • Renal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in pediatric renal disease. • Renal RAS activation plays a key role of renal development during gestation. What is New : • Plasma (pro)renin and soluble (pro)renin receptor (s(P)RR) levels in cord blood were significantly higher in preterm neonates than in full-term neonates. • Immunohistochemical analysis of kidney tissue indicated that renal expression levels of (P)RR in neonates were stronger than in minor glomerular abnormalities.

  14. Increased plasma fibronectin concentrations in obesity

    DEFF Research Database (Denmark)

    Andersen, T; Dejgaard, A; Astrup, A

    1987-01-01

    In 23 morbidly obese patients we investigated the influence of a large weight loss (30.6 kg, range 17.5-90.8) on the plasma fibronectin concentrations. Further, changes in plasma fibronectin were related to serum insulin levels and to liver biochemistry. Between the measurements patients had been...

  15. Plasma renin activity and risk of cardiovascular and mortality outcomes among individuals with elevated and nonelevated blood pressure

    Directory of Open Access Journals (Sweden)

    Simran K. Bhandari

    2016-12-01

    Conclusion: Higher PRA levels demonstrated increased risk for ischemic heart events and congestive heart failure and a trend toward higher mortality among individuals with SBP ≥ 140 mmHg but not among those with SBP < 140 mmHg.

  16. Transgenic mice overexpressing renin exhibit glucose intolerance and diet-genotype interactions

    Directory of Open Access Journals (Sweden)

    Sarah J. Fletcher

    2013-01-01

    Full Text Available Numerous animal and clinical investigations have pointed to a potential role of the renin-angiotensin system (RAS in the development of insulin resistance and diabetes in conditions of expanded fat mass. However, the mechanisms underlying this association remain unclear. We used a transgenic mouse model overexpressing renin in the liver (RenTgMK to examine the effects of chronic activation of RAS on adiposity and insulin sensitivity. Hepatic overexpression of renin resulted in constitutively elevated plasma angiotensin II (4-6-fold increase vs. wild type. Surprisingly, RenTgMK mice developed glucose intolerance despite low levels of adiposity and insulinemia. The transgenics also had lower plasma triglyceride levels. Glucose intolerance in transgenic mice fed a low-fat diet was comparable to that observed in high fat-fed wild type mice. Glucose intolerance was exacerbated by high-fat feeding, only in female transgenic mice. These studies demonstrate that overexpression of renin and associated hyperangiotensinemia impair glucose tolerance in a diet-dependent manner and further support a consistent role of RAS in the pathogenesis of diabetes and insulin resistance, independent of changes in fat mass.

  17. Possible contribution of(pro)renin receptor to development of gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Kanako; Bokuda; Atsuhiro; Ichihara

    2014-01-01

    (Pro)renin receptor [(P)RR], a receptor for renin and prorenin, was first cloned in 2002. Since then, the pathophysiological roles of(P)RR have been growing concerns.(P)RR binds renin and prorenin, with two important consequences, nonproteolytic activation of prorenin, leading to the tissue renin-angiotensin system activation and the intracellular signalings. It is now also known to play an important role as vacuolar H+-ATPase associated protein, involving in Wnt signaling, main component of embryonic development. Extracellular domain of full-length(P)RR is cleaved in golgi-complex forming soluble(P)RR [s(P)RR]. The s(P)RR is now possible to be measured in human blood and urine. It is now measured in different pathophysiological states, and recent study showed that elevated plasma s(P)RR levels in the early stage of pregnancies are associated with higher incidence of gestational diabetes mellitus later in the pregnancies. Plasma s(P)RR levels of neonates are known to be higher than that of adults. It was also shown that, increased s(P)RR concentrations in cord blood, associated with a lower small for gestational age birth likelihood. These data suggests the involvement of(P)RR in embryo’s growth. In thisreview article, we attempt to figure out the possible pathophysiological roles of the(P)RR in maternal glucose intolerance and embryo’s growth, through reviewing previous studies.

  18. Real-time imaging of renin release in vitro.

    Science.gov (United States)

    Peti-Peterdi, János; Fintha, Attila; Fuson, Amanda L; Tousson, Albert; Chow, Robert H

    2004-08-01

    Renin release from juxtaglomerular granular cells is considered the rate-limiting step in activation of the renin-angiotensin system that helps to maintain body salt and water balance. Available assays to measure renin release are complex, indirect, and work with significant internal errors. To directly visualize and study the dynamics of both the release and tissue activity of renin, we isolated and perfused afferent arterioles with attached glomeruli dissected from rabbit kidneys and used multiphoton fluorescence imaging. Acidotropic fluorophores, such as quinacrine and LysoTrackers, clearly and selectively labeled renin granules. Immunohistochemistry of mouse kidney with a specific renin antibody and quinacrine staining colocalized renin granules and quinacrine fluorescence. A low-salt diet for 1 wk caused an approximately fivefold increase in the number of both individual granules and renin-positive granular cells. Time-lapse imaging showed no signs of granule trafficking or any movement, only the dimming and disappearance of fluorescence from individual renin granules within 1 s in response to 100 microM isoproterenol. There appeared to be a quantal release of the granular contents; i.e., an all-or-none phenomenon. Using As4.1 cells, a granular cell line, we observed further classic signs of granule exocytosis, the emptying of granule content associated with a flash of quinacrine fluorescence. Using a fluorescence resonance energy transfer-based, 5-(2-aminoethylamino)naphthalene-1-sulfonic acid (EDANS)-conjugated renin substrate in the bath, an increase in EDANS fluorescence (renin activity) was observed around granular cells in response to isoproterenol. Fluorescence microscopy is an excellent tool for the further study of the mechanism, regulation, and dynamics of renin release.

  19. Prognostic value of plasma catecholamines, plasma renin activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure: comparison with clinical evaluation, ejection fraction, and exercise capacity

    DEFF Research Database (Denmark)

    Madsen, B K; Keller, N; Christiansen, E

    1995-01-01

    carried significant, independent prognostic information in a multivariate analysis: left ventricular ejection fraction (P = .03), plasma noradrenaline at rest (P = .009), New York Heart Association class III + IV (P = .005), increase in heart rate during exercise ... creatinine > 121 mumol/L (P = .004), and serum urea > 7.6 mmol/L (P = .007). Patients with congestive heart failure have a poor survival despite intensive medical treatment. Plasma catecholamines and plasma atrial natriuretic peptide are elevated at rest and rises further during exercise; the increase......Survival in congestive heart failure is related to plasma catecholamines and atrial natriuretic peptide at rest, but the prognostic importance of changes during exercise is unknown. The aim of this study was to evaluate the prognostic value of catecholamines and atrial natriuretic peptide at rest...

  20. Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension.

    Science.gov (United States)

    Shinohara, Keisuke; Liu, Xuebo; Morgan, Donald A; Davis, Deborah R; Sequeira-Lopez, Maria Luisa S; Cassell, Martin D; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D

    2016-12-01

    The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving the expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril, or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of angiotensin-II type 1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin, which was dependent on angiotensin-II type 1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventrolateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension. © 2016 American Heart Association, Inc.

  1. Direct radio-immunoassay of renin substrate: effect of converting enzyme inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Metsaerinne, Kaj; Rosenloef, Katarina; Groenhagen-Riska, Carola; Fyhrquist, Frej

    1988-02-01

    A direct radio-immunoassay (RIA) for renin substrate (RS) was compared to enzymatic (indirect) assay. In normal subjects, a significant, albeit weak, correlation between the methods was seen. In hypertensive patients with different levels of plasma renin activity (PRA), RS concentration measured by both assays increased with increasing PRA, and for patients with PRA > 10 ..mu..g AI/l/h, direct assay gave significantly higher RS values (55%), compared to the enzymatic assay, indicating consumption of RS by increasing plasma renin and production rate of RS with increasing PRA. In 11 patients with renovascular hypertension, treatment with angiotensin-converting enzyme (ACE) inhibitor, lisinopril, resulted in a significant increase in PRA, accompanied by a decrease in RS measured by enzymatic assay. No change in RS measured by direct RIA was noticed. The results suggest that ACE inhibition may not have an effect upon RS production and that its effect on plasma RS is limited to a reduction of intact RS measured by the enzymatic assay.

  2. Increased plasma carnitine concentrations in preeclampsia

    NARCIS (Netherlands)

    Thiele, IGI; Niezen-Koning, KE; van Gennip, AH; Aarnoudse, JG

    2004-01-01

    OBJECTIVE: Preeclampsia is associated with abnormal lipid metabolism, including fatty acid metabolism. Carnitine plays an indispensable role in the oxidation of fatty acids. The aim of the study was to evaluate the possible role of abnormal fatty add oxidation in preeclampsia by comparing plasma car

  3. 心肺复苏后血浆肾素活性与醛固酮分离现象的再研究%An analysis about the separation of plasma renin activity and aldosterone in patients with cardio-pulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    朱丽; 黄佳; 袁琦松; 周厚荣

    2016-01-01

    Objective To investigate the effect of separation of plasma renin activity and aldo⁃sterone on return of spontaneous circulation(ROSC)in patients with cardiopulmonary resuscitation (CPR). Method Thirty patients whose physical examinations were normal were randomly divided into group N; a total of 60 patients with sudden cardiac arrest who were treated with CPR were divided into two groups according to the effect of CPR, 28 patients with restoration of spontaneous circulation were group S, and 32 patients without restoration of spontaneous circulation were group U, at the Guizhou Province People's Hospital from January 2015 to December 2015. Peripheral venous blood of patients with CA 30 minites after CPR was collected, in order to test the plasma renin activity, aldosterone, serum potassium and sodium concentration and to compare each index between different groups. Results ①Compared to group N, plasma renin activity and aldosterone were obviously increased in group S and group U; and plasma renin activity and aldosterone in group U were higher than group S; the difference was statistically significant(P<0.05). ②The proportion of the separation of plasma renin activity and aldosterone in group S was lower than that in group U; the rate of ROSC in the group without separation of aldosterone was higher than the group with separation of aldosterone(2=4.63, P<0.05); and the level of serum potassium concentration in group with separation of aldosterone was higher than that in group with⁃out separation of aldosterone(P<0.01); the level of plasma sodium concentration in group without sepa⁃ration of aldosterone was lower than group with separation of aldosterone(P<0.01). Conclusion The phenomenon of the separation of renin activity and aldosterone exists in the patients who are treated with cardiopulmonary resuscitation, and the separation of plasma renin activity and aldosterone might induce hyponatremia and hyperkalemia, which is the disadvantage of

  4. Optimization of orally bioavailable alkyl amine renin inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhenrong; Cacatian, Salvacion; Yuan, Jing; Simpson, Robert D.; Jia, Lanqi; Zhao, Wei; Tice, Colin M.; Flaherty, Patrick T.; Guo, Joan; Ishchenko, Alexey; Singh, Suresh B.; Wu, Zhongren; McKeever, Brian M.; Scott, Boyd B.; Bukhtiyarov, Yuri; Berbaum, Jennifer; Mason, Jennifer; Panemangalore, Reshma; Cappiello, Maria Grazia; Bentley, Ross; Doe, Christopher P.; Harrison, Richard K.; McGeehan, Gerard M.; Dillard, Lawrence W.; Baldwin, John J.; Claremon, David A. (Vitae); (GSKPA)

    2010-09-17

    Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC{sub 50} of 0.83 nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10 mg/kg resulted in >20 h reduction of blood pressure in a double transgenic rat model of hypertension.

  5. [Renin-angiotensin-aldosterone system in diabetes insipidus].

    Science.gov (United States)

    Kirillov, G; Ankov, V

    1980-01-01

    Plasma renin activity (PR) and plasma aldosterone level (PA) were investigated in 38 patients with central diabetes incipidus under conditions of standard sodium intake and after a three-day reduction of sodium in the diet with an additional furosemide load. Blood was recovered for examination in the morning under complete rest and after a two-hour slow walk. Apparently healthy volunteers (20) served as control. The PR and PA content was determined by the radioimmunological method. Not only the basic, but also the stimulated renin secretion was increased in patients with diabetes incipidus. The basic PA level was significantly diminished; after stimulation its level did not differ from that in healthy persons. At rest and with decreased sodium intake the patients displayed two types of PR activity: in some (n=18) there was no elevation, and in other (n=19) the rise was marked. It is supposed that in diabetes incipidus hyperreninemia was compensatory, directed to water retention in the organism; apparently it participated in the mechanism of hypovolemic thirst. An unusual combination of increased PR with diminished PA level is described for the first time.

  6. Renin-angiotensin system in sepsis.

    Science.gov (United States)

    Hilgenfeldt, U; Kienapfel, G; Kellermann, W; Schott, R; Schmidt, M

    1987-01-01

    The time course of the components of the renin-angiotensin system was investigated in the plasma of three patients on the intensive care unit. Two of them, which were both polytraumatized, suffered from adult respiratory distress syndrome (ARDS). All patients had sepsis and impaired pulmonary and renal function. Plasma samples were investigated for up to two weeks, in which time all three patients showed a decrease in their angiotensin converting enzyme (ACE) plasma concentration. Two of the patients with deteriorating renal function had three to four times elevated angiotensinogen (Ao) plasma levels, which were measured by both the direct and indirect radioimmunoassay. The ratio of the mean values between both assays was 1:1 in two patients and shifted to higher values in the direct assay in the third patient. This suggests that higher amounts of des-AngI-angiotensinogen were present in the latter patient, because "inactive" Ao is also detected by the direct assay. The decrease in active Ao may be caused by an up to twenty times elevated plasma renin activity (PRA). The PRA was correlated with the angiotensin I (AngI) plasma levels. However, at PRA values higher than 200 pmol AngI/ml/h this correlation decreased because of the rapid substrate consumption. In addition there was a good correlation between AngI and AngII plasma levels in two patients which could not be observed in the patient with the highest PRA and AngII values. A relationship between plasma ACE concentration and AngII formation could not be observed. Thus in two of the three septic patients the components of the renin angiotensin system were extremely stimulated at very low blood pressure values. These data show, that it is reasonable to follow the time course of the components of the renin angiotensin system in single patients. In addition it is demonstrated that the direct measurement of Ao is a valid supplement in the diagnosis of the renin angiotensin system.

  7. The effects of antidiuretic hormone and state of potassium balance on the renin-angiotensin system in rats with diabetes insipidus.

    Science.gov (United States)

    Fernández-Repollet, E; Maldonado, M M; Opava-Stitzer, S

    1982-02-01

    1. The influence of ADH and the state of potassium balance on the renin-angiotensin system was studied in rats with hereditary diabetes insipidus (DI rats). 2. Plasma renin concentration in DI rats was higher than in control Long-Evans rats. 3. Spontaneous reversal of the hypokalaemia normally found in DI rats did not reduce plasma renin concentration (p.r.c.), suggesting that potassium deficiency does not contribute significantly to the elevation of p.r.c. in DI rats. Similarly, a low potassium diet failed to further increase p.r.c. in DI rats. 4. In contrast, the p.r.c. of DI rats was significantly diminished by a high potassium intake both in the presence and absence of ADH. A highly significant inverse correlation was found between p.r.c. and urinary potassium excretion in both ADH-treated and untreated DI rats on low, normal and high potassium diets. 5. Plasma renin concentration was significantly lower in ADH-treated than in untreated DI rats on a high potassium intake, suggesting that the inhibitory effects of ADH and potassium are additive. 6. ADH consistently reduced p.r.c. in DI rats independent of the state of potassium balance. 7. ADH and potassium may inhibit renin secretion via different mechanisms of action.

  8. Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations

    OpenAIRE

    Fowler, Jason D.; Krueth, Stacy B.; Bernlohr, David A.; Katz, Stephen A.

    2009-01-01

    The renin-angiotensin system (RAS) has been implicated in a variety of adipose tissue functions, including tissue growth, differentiation, metabolism, and inflammation. Although expression of all components necessary for a locally derived adipose tissue RAS has been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two ...

  9. Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors

    DEFF Research Database (Denmark)

    Hautmann, Matthias; Friis, Ulla G; Desch, Michael

    2007-01-01

    concentration was significantly lower in PAC1-/- compared with their wild-type littermates under control conditions as well as under a low- or high-salt diet and under treatment with the angiotensin-converting enzyme inhibitor ramipril, whereas no differences in plasma renin concentration between the genotypes......), because PACAP (1-27) applied in concentrations in the physiologic range (10 and 100 pmol/L) did not enhance renin release from isolated kidneys of PAC1 receptor knockout mice (PAC1-/-), whereas it stimulated renin release 1.38- and 2.5-fold in kidneys from wild-type mice. Moreover, plasma renin...... were detectable after water deprivation. These data show that PACAP acting on PAC1 receptors potently stimulates renin release, serving as a tonic enhancer of the renin system in vivo....

  10. The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo.

    Science.gov (United States)

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki; Pavenstädt, Hermann; Narumiya, Shuh; Jensen, Boye L; Nüsing, Rolf M

    2012-11-15

    Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been shown to be prerequisites for renal renin release after Na(+) deprivation. To answer the question of whether EP4 receptor type of PGE(2) mediates renin regulation under a low-salt diet, we examined renin regulation in EP4(+/+), EP4(-/-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+) excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and plasma electrolytes remained unchanged. EP4(-/-) exhibited a similar attenuation of Na(+) excretion; however, diuresis and K(+) excretion were enhanced, and plasma Na(+) concentration was higher, whereas plasma K(+) concentration was lower compared with control diet. There were no significant differences between EP4(+/+) and EP4(-/-) mice in blood pressure, creatinine clearance, and plasma antidiuretic hormone (ADH) concentration. Following salt restriction, plasma renin and aldosterone concentrations and kidney renin mRNA level rose significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with EP4 antagonist ONO-AE3-208. In the latter two groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss.

  11. Direct renin inhibition in chronic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

    2013-01-01

    that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...... kidney disease by reporting of the studies published so far as well as perspective on the future possibilites....

  12. Pharmacokinetics, pharmacodynamics, and tolerability of ACT-077825, a new direct renin inhibitor after multiple-ascending doses in healthy subjects.

    Science.gov (United States)

    Nicolas, Laurent B; Gutierrez, Marcelo; Binkert, Christoph; Dingemanse, Jasper

    2013-01-01

    This study was conducted to characterize the multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-077825, a new direct renin inhibitor, in healthy male subjects. In this single-center, double-blind, placebo-controlled, active-controlled (20 mg of enalapril), randomized multiple-ascending dose study, ACT-077825 was administered once a day. for 7 days in the 50-1000 mg dose range to sodium- and potassium-restricted subjects. ACT-077825 pharmacokinetics on days 1 and 7 were characterized by dose-proportional increases in Cmax and AUCτ. At steady state, accumulation was modest (1.5- to 1.7-fold). Enalapril caused an increase in plasma active renin concentration and plasma renin activity (PRA). ACT-077825 dose dependently increased active renin on days 1 and 7 and inhibited PRA dose dependently only on day 1. On day 7, the maximal PRA inhibition was attained after 250 mg of ACT-077825. In contrast to enalapril, ACT-077825 did not induce any consistent lowering effect on blood pressure when compared with placebo. Of the reported adverse events, diarrhea, headache, and postural dizziness were more frequent. The incidence of diarrhea was greater in the 1000-mg group and a dose of 500 mg of ACT-077825 was identified as the maximum tolerated dose. Overall, pharmacokinetic, pharmacodynamic, and tolerability profiles warrant the further investigation of ACT-077825 in patients with hypertension.

  13. High salt intake damages the heart through activation of cardiac (pro renin receptors even at an early stage of hypertension.

    Directory of Open Access Journals (Sweden)

    Yuka Hayakawa

    Full Text Available It has not yet been fully elucidated whether cardiac tissue levels of prorenin, renin and (PRR are activated in hypertension with a high salt intake. We hypothesized that a high salt intake activates the cardiac tissue renin angiotensin system and prorenin-(prorenin receptor system, and damages the heart at an early stage of hypertension.Wistar Kyoto rats (WKY and spontaneously hypertensive rats (SHR received regular (normal-salt diet, 0.9% and high-salt (8.9% chow for 6 weeks from 6 to 12 weeks of age. The systolic blood pressure, plasma renin activity (PRA and plasma angiotensin II concentration were measured, and the protein expressions of prorenin, (prorenin receptor, angiotensinogen, angiotensin II AT1 receptor, ERK1/2, TGF-β, p38MAPK and HSP27 in the myocardium were investigated. The cardiac function was assessed by echocardiography, and histological analysis of the myocardium was performed.The high-salt diet significantly increased the systolic blood pressure, and significantly reduced the PRA and plasma angiotensin II concentration both in the WKYs and SHRs. Cardiac expressions of prorenin, renin, (PRR, angiotensinogen, angiotensin II AT1 receptor, phosphorylated (p-ERK1/2, p-p38MAPK, TGF-β and p-HSP27 were significantly increased by the high salt diet both in the WKYs and SHRs. The high-salt diet significantly increased the interventricular septum thickness and cardiomyocyte size, and accelerated cardiac interstitial and perivascular fibrosis both in the WKYs and SHRs. On the other hand, dilatation of left ventricular end-diastolic dimension and impairment of left ventricular fractional shortening was shown only in salt loaded SHRs.The high-salt diet markedly accelerated cardiac damage through the stimulation of cardiac (PRR and angiotensin II AT1 receptor by increasing tissue prorenin, renin and angiotensinogen and the activation of ERK1/2, TGF-β, p38MAPK and HSP27 under higher blood pressure.

  14. Renin-angiotensin system blockade: Its contribution and controversy.

    Science.gov (United States)

    Miyajima, Akira; Kosaka, Takeo; Kikuchi, Eiji; Oya, Mototsugu

    2015-08-01

    Angiotensin II is a key biological peptide in the renin-angiotensin system that regulates blood pressure and renal hemodynamics, and extensive experimental studies have shown that angiotensin II promotes diverse fibrotic changes and induces neovascularization in several inflammatory diseases. It is known that angiotensin II can be controlled using renin-angiotensin system blockade when angiotensin II is the main factor inducing a particular disease, and renin-angiotensin system blockade has assumed a central role in the treatment of inflammatory nephritis, cardiovascular disorders and retinopathy. In contrast, renin-angiotensin system blockade was found to have not only these effects but also other functions, such as inhibition of cancer growth, angiogenesis and metastasis. Numerous studies have sought to elucidate the mechanisms and support these antitumor effects. However, a recent meta-analysis showed that renin-angiotensin system blockade use might in fact increase the incidence of cancer, so renin-angiotensin system blockade use has become somewhat controversial. Although the renin-angiotensin system has most certainly made great contributions to experimental models and clinical practice, some issues still need to be resolved. The present review discusses the contribution and controversy surrounding the renin-angiotensin system up to the present time.

  15. Control of the renal renin system by local factors

    DEFF Research Database (Denmark)

    Wagner, C; Jensen, B L; Krämer, B K

    1998-01-01

    prostanoid, both stimulate renin secretion and renin gene expression by activating cAMP formation in JG cells. Although the direct effect of NO on JG cells is less clear, its overall effect in vivo seems to be to stimulate the renin system. Evidence is emerging that stimulation by NO is related to the c......AMP pathway, and cGMP-induced inhibition of cAMP-phosphodiesterase III (PDE-III) may mediate this effect. ETs, on the other hand, appear to inhibit the renin system, in particular in those pathways activated by cAMP, acting via Ca2+- and protein kinase C-related mechanisms. There is increasing evidence...... that both NO and PGs could be involved in the physiological regulatory mechanisms by which salt intake affects the renin system....

  16. Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

    Directory of Open Access Journals (Sweden)

    Fernanda S. Zamo

    2010-01-01

    Full Text Available BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1 hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate; 2 left ventricular hypertrophy; and 3 local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13 and adult (n=12. Hemodynamic signals (blood pressure, heart rate, blood pressure variability (BPV and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g, by myocyte diameter (μm and by relative fibrosis area (RFA, %. ACE and ACE2 activities were measured by fluorometry (UF/min, and plasma renin activity (PRA was assessed by a radioimmunoassay (ng/mL/h. Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU. RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent

  17. Factors affecting the aldosterone/renin ratio.

    Science.gov (United States)

    Stowasser, M; Ahmed, A H; Pimenta, E; Taylor, P J; Gordon, R D

    2012-03-01

    Although the aldosterone/renin ratio (ARR) is the most reliable screening test for primary aldo-steronism, false positives and negatives occur. Dietary salt restriction, concomitant malignant or renovascular hypertension, pregnancy and treatment with diuretics (including spironolactone), dihydropyridine calcium blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists can produce false negatives by stimulating renin. We recently reported selective serotonin reuptake inhibitors lower the ratio. Because potassium regulates aldosterone, uncorrected hypokalemia can lead to false negatives. Beta-blockers, alpha-methyldopa, clonidine, and nonsteroidal anti-inflammatory drugs suppress renin, raising the ARR with potential for false positives. False positives may occur in patients with renal dysfunction or advancing age. We recently showed that (1) females have higher ratios than males, and (2) false positive ratios can occur during the luteal menstrual phase and while taking an oral ethynylestradiol/drospirenone (but not implanted subdermal etonogestrel) contraceptive, but only if calculated using direct renin concentration and not plasma renin activity. Where feasible, diuretics should be ceased at least 6 weeks and other interfering medications at least 2 before ARR measurement, substituting noninterfering agents (e. g., verapamil slow-release±hydralazine and prazosin or doxazosin) were required. Hypokalemia should be corrected and a liberal salt diet encouraged. Collecting blood midmorning from seated patients following 2-4 h upright posture improves sensitivity. The ARR is a screening test only and should be repeated once or more before deciding whether to proceed to confirmatory suppression testing. Liquid chromatography-tandem mass spectrometry aldosterone assays represent a major advance towards addressing inaccuracies inherent in other available methods.

  18. Studies on Renin Stimulation in Normal Controls and in Patients with Essential Hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Chang Soon; Choe, Kang Won; Lee, Hong Kyu; Lee, Jung Sang [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1978-03-15

    To find out a convenient and reliable method of detecting low renin status, we employed intravenous furosemide injection as a stimulatory maneuver. The results thus obtained were compared with those from the postural stimuli and basal plasma renin activity (PRA) in relation to sodium excretion. Intravenous furosemide test was performed in 66 control subjects and 44 patients with essential hypertension. The results were as follow; 1) Mean PRA in control subjects rose from 2.5+-1.95 ng/ml/hr (basal) to 4.5+-2.51, 5.2+-2.49 and 4.2+-2.44 ng/ml/hr at 1, 2 and 3 hrs after IV injection. One-hour response is more convenient in clinical practice. 2) Postural stimuli by assuming an upright posture for 3 hrs gave rise to considerable increase in PRA (4.0+-2.92 from 2.4+-1.85), but we found it less convenient than stimulation with furosemide. 3) The increase in PRA was much less marked in patients with essential hypertension as a whole (2.9+-2.75). Hyporesponsiveness to furosemide stimuli was found in 34.1%. Of these hyporesponders, a third had a normal basal PRA, indicating the need for this kind stimulatory procedure. 4) Younger age group showed greater renin responsiveness than older age group after furosemide stimuli. Likewise mean age of low renin patients (52.9+-5.38 years old) was significantly higher than that of high and normal renin patients (44.1+-13.78 years old).

  19. Are plasma renin activity and aldosterone levels useful as a screening test to differentiate between unilateral and bilateral renal artery stenosis in hypertensive patients?

    Science.gov (United States)

    Kotliar, Carol; Inserra, Felipe; Forcada, Pedro; Cavanagh, Elena; Obregon, Sebastián; Navari, Carlos; Castellaro, Carlos; Sánchez, Ramiro

    2010-03-01

    To evaluate the serum aldosterone (Ald)/plasmatic renin activity (PRA) ratio as a surrogate marker of renin-angiotensin-aldosterone system status in unilateral (Uni)- and bilateral (Bi)-renal artery stenosis (RAS). Seven hundred and eight hypertensive patients (HTP) were studied. Intermediate and high pretest risk of RAS was detected in 66 HTP who subsequently underwent renal gadolinium-enhanced magnetic resonance and arteriography. After application of exclusion criteria 51 HTP remained: 16 with Uni-RAS, 16 with Bi-RAS and 19 essential hypertensives with normal arteries. Nineteen normotensive individuals were also studied. Ald and PRA were determined before and after stenosis resolution by balloon angioplasty and stent implantation. Ald/PRA (ng/dl per (ng/ml per h(-1))) was markedly high in Bi-RAS (5.92 +/- 2.30, P HTP with Uni-RAS or Bi-RAS. Studies with a higher number of patients will allow exploration of the usefulness of pharmacologic aldosterone blockade in Bi-RAS, and to assess the relevance of Ald/PRA to differentiate Uni-RAS from Bi-RAS.

  20. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    Science.gov (United States)

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice.

  1. Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats.

    Science.gov (United States)

    Kim, Yang Gyun; Lee, Sang Ho; Kim, Se-Yun; Lee, Arah; Moon, Ju Young; Jeong, Kyung-Hwan; Lee, Tae Won; Lim, Sung Jig; Sohn, Il Suk; Ihm, Chun-Gyoo

    2016-07-01

    The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.

  2. 血浆醛固酮/肾素活性比值在原发性醛固酮增多症诊断中的价值%The Diagnosis Value of Plasma Aldosterone/renin Activity Ratio in Primary Aldosteronism

    Institute of Scientific and Technical Information of China (English)

    刘慧光; 任建伟; 陈彦民

    2011-01-01

    目的:探讨血浆醛固酮/肾素活性比值(ARR)在原发性醛固酮增多症(PA)诊断中的临床价值.方法:选择我院收治的高血压患者460例,空腹采血后采用放射免疫法测定患者醛固酮和肾素水平,并计算血浆醛固酮/肾素活性比值.对其中疑诊为原发性醛固酮增多症的患者再行肾上腺薄层CT扫描,并行血液生化和血清钾检测.结果:460例患者中,ARR>25者56例,经肾上腺薄层CT扫描、血液生化和血清钾检测后确诊为原发性醛固酮增多症者48例.ARR应用于原发性醛固酮增多症的检出率为10.43%,诊断符合率为85.71%.48例患者中合并低血钾者18例,占37.5%.结论:血浆醛固酮/肾素活性比值在临床的应用可使高血压人群中原发性醛固酮增多症的检出率明显增加,具有重要的临床价值,应作为重度高血压和难治性高血压患者的常规检查项目.%Objective: To investigate the diagnosis value of plasma aldosterone/renin activity ratio (ARR) in primary aldosteronism.Methods: 460 patients with hypertension were collected, after fasting blood measured by radioimmunoassay in patients with aldosterone and renin levels, and calculate the plasma aldosterone/renin activity ratio.Checking the patients which was suspected with primary aldosteronism by CT scan of adrenal thin, blood biochemistry and serum potassium.Results: In 460 patients, there were 56 patients' ARR>25.The CT scan, adrenal thin layer blood biochemical and potassium diagnosed after detecting primary aldosteronism in 48 cases.Detection rate was 10.43%, diagnostic rate was 85.71%.18 patients combined hypokalemia in 48 patients (37.5%).Conclusion: Plasma aldosterone/renin activity ratio in the clinical application can significantly increase the detection rate in hypertensives with primary aldosteronism, it has important clinical value, should be severe hypertension and refractory hypertension in patients with routine examination project.

  3. Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade

    DEFF Research Database (Denmark)

    Mølstrøm, Simon; Larsen, Nils Heden; Simonsen, Jane Angel;

    2008-01-01

    and renal excretion during slow saline loading at constant plasma sodium con-centration (Na-loading: 12 micromol Na(+) kg(-1) min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na......-loading decreased plasma renin (PRC) by 1/3, AngII by 1/2, and aldosterone (pAldo) by 2/3, (all pmetoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16+/-2 to 71...

  4. Renoprotection, renin inhibition, and blood pressure control: the impact of aliskiren on integrated blood pressure control

    Directory of Open Access Journals (Sweden)

    Haroon-Ur Rashid

    2010-10-01

    Full Text Available Haroon-Ur RashidDepartment of Cardiology, Baylor College of Medicine, Texas Heart Institute, Houston, TX, USAAbstract: Hypertension (HTN is an important factor in progressive loss of renal function. The kidney can be both a contributor to and a target of HTN. The functional integrity of the kidney is vital for the maintenance of cardiovascular homeostasis. Chronic activation of the renin system causes HTN and, ultimately, end-organ damage. Direct renin inhibitors (DRIs inhibit plasma renin activity (PRA, thereby preventing the conversion of angiotensinogen to angiotensin I; consequently, the levels of both Ang I and Ang II are reduced. There is no compensatory increase in PRA activity with DRIs as seen with angiotensin-converting enzyme inhibitors (ACEIs or angiotensin receptor blockers (ARBs. There are reasons to speculate that renin inhibition might prove to be a superior strategy for blocking the renin–angiotensin–aldosterone system compared with ACEIs or ARBs. Evidence for the efficacy of aliskiren (a DRI is considered to be relatively strong, based on published, short-term, double-blind, randomized, controlled trials showing that aliskiren is as effective as other antihypertensive agents in reducing blood pressure (BP, with no rebound effects on BP after treatment withdrawal. When combined with diuretics, fully additive BP reduction is seen. When given with an ACEI or ARB, aliskiren produces significant additional BP reduction indicative of complimentary pharmacology and more complete renin–angiotensin system blockade.Keywords: aliskiren, direct renin inhibitor, angiotensin-converting enzyme inhibitor, ACE inhibitor, angiotensin II receptor blocker, chronic kidney disease, hypertension, diabetes mellitus

  5. Cortisol-induced inhibition of ovine renin and aldosterone responses to hypotension

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.E.; Silbiger, J.

    1987-03-01

    Previous studies from this laboratory have demonstrated that in preterm fetal sheep increases in plasma cortisol (F) concentration equal in amplitude to fetal F stress responses suppress plasma renin activity (PRA). The purpose of this study was to investigate the possibility that this negative interaction exists in adult sheep. Cortisol was measured by radioimmunoassay. Five conscious ewes with chronically prepared carotid arterial loops were infused intravenously with F or vehicle for 5 h. One hour after the end of F or vehicle infusion, renin secretion was stimulated by hypotension produced by infusion of sodium nitroprusside. F infusion increased plasma F; during vehicle infusion plasma F did not change. F infusion decreased hematocrit from 29 +/- 2 to 26 +/- 1%. Basal PRA in vehicle- and F-infused groups were 0.4 +/- 0 and 0.2 +/- 0.1 ng angiotensin I-ml/sup -1/-h/sup -1/ and did not change. In vehicle-infused ewes, PRA increased from 0.4 +/- 0 to 4.6 +/- 0.4 and plasma aldosterone from 26.0 +/- 1.0 to 173.1 +/- 21.8 pg/ml, while in F-infused ewes, PRA increased from 0.2 +/- 1 to 3.3 +/- 0.4 ng angiotensin I-ml/sup -1/-h/sup -1/ and aldosterone from 25.0 +/- 0 to 48.2 +/- 23.2 pg/ml, significantly smaller responses. These results suggest that repeated stress may modulate the responses of the renin-angiotensin system in this species.

  6. Prostaglandins, renin, aldosterone, and catecholamines in preeclampsia.

    Science.gov (United States)

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1983-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  7. Chronic activation of plasma renin is log-linearly related to dietary sodium and eliminates natriuresis in response to a pulse change in total body sodium

    DEFF Research Database (Denmark)

    Kjolby, Mads; Bie, Peter

    2008-01-01

    data, we demonstrate that RAAS variables are log-linearly related to sodium intake over a >250-fold range in sodium intake, defining dietary sodium function lines that are simple measures of the sodium sensitivity of the RAAS. The dietary function line for plasma ANG II concentration increases from...... theoretical zero at a daily sodium intake of 17 mmol Na/kg (intercept) with a slope of 16 pM increase per decade of decrease in dietary sodium intake.......Responses to acute sodium loading depend on the load and on the level of chronic sodium intake. To test the hypothesis that an acute step increase in total body sodium (TBS) elicits a natriuretic response, which is dependent on the chronic level of TBS, we measured the effects of a bolus of Na...

  8. Renin and aldosterone at high altitude in man.

    Science.gov (United States)

    Keynes, R J; Smith, G W; Slater, J D; Brown, M M; Brown, S E; Payne, N N; Jowett, T P; Monge, C C

    1982-01-01

    Measurements have been made of hormonal changes relevant to salt and water balance during prolonged exposure to hypoxia to improve our understanding of the syndrome of acute mountain sickness. We have attempted to delineate the detailed inter-relationships between the renin-aldosterone and the vasopressin systems by a metabolically controlled study, involving an orthostatic stress (45 degrees head-up tilt) and an injection of a standard dose of ACTH to test adrenal responsiveness. Three Caucasian medical students underwent a 7-day equilibration at 150 m (Lima, Peru), followed by a 6-day sojourn at 4350 m (Cerro de Pasco, Peru) and a final 7 days at 150 m. Measurements were made of sodium and potassium balance, body weight and the 24-h renal excretion of vasopressin, cortisol and aldosterone 18-glucuronide. These variables showed little change, except for that of aldosterone 18-glucuronide, which fell sharply at altitude and rebounded even more sharply on return to sea level. At altitude, basal plasma levels of renin activity and aldosterone fell, and the response to orthostasis was attenuated, but the fall of plasma renin activity, as compared to plasma aldosterone, was delayed; on return to sea level this dissociation was exacerbated with the return of normal renin responsiveness lagging behind that of aldosterone. We suggest that unknown factors which dissociate the orthodox renin-aldosterone relationship, other than the activity of the angiotensin I-converting enzyme, are operative on exposure to hypoxia.

  9. Active renin mass concentration to determine aldosterone-to-renin ratio in screening for primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Corbin F

    2011-07-01

    Full Text Available François Corbin1, Pierre Douville2, Marcel Lebel3 1Division of Biochemistry, l'Université de Sherbrooke, Sherbrooke, Quebec, Canada; 2Division of Biochemistry; 3Division of Nephrology, L'Hôtel-Dieu de Québec Hospital and l'Université Laval, Quebec, CanadaBackground: Active renin mass concentration (ARC is independent of the endogenous level of angiotensinogen, and less variable and more reproducible than plasma renin activity. Reference values for the aldosterone-to-renin ratio (ARR using ARC are still undefined. The objective of the present study was to determine the threshold of ARR using ARC measurement to screen for primary aldosteronism.Methods: A total of 211 subjects were included in the study, comprising 78 healthy normotensive controls, 95 patients with essential hypertension, and 38 patients with confirmed primary aldosteronism (20 with surgery-confirmed aldosterone-producing adenoma and 18 with idiopathic adrenal hyperplasia. Blood samples were drawn from ambulatory patients and volunteers in the mid-morning without specific dietary restriction for measuring plasma aldosterone concentration, ARC, and serum potassium.Results: Most normotensive controls and essential hypertension patients had ARR results below 100 pmol/ng, a value which corresponded to 3.3 times the median of these two groups.Conclusion: Patients with ARR values above this level should be considered for further investigation (confirmatory tests or for repeat testing should ARR values be borderline. This study indicates that ARC can be used reliably in determining ARR for primary aldosteronism screening.Keywords: primary aldosteronism, active renin mass concentration, aldosterone-to-renin ratio

  10. Influence of the adenosine A1 receptor on blood pressure regulation and renin release

    DEFF Research Database (Denmark)

    Brown, Russell D.; Thorén, Peter; Steege, Andreas

    2006-01-01

    The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD......) diets for a minimum of 10 days before telemetric blood pressure and urinary excretion measurements in metabolic cages. On the NS diet, daytime and nighttime mean arterial blood pressure (MAP) was 7-10 mmHg higher in A1R-/- than in A1R+/+ mice. HS diet did not affect the MAP in A1R-/- mice....... The elevated plasma renin concentrations found in the A1R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion....

  11. Clinical relevance of urinary angiotensinogen and renin as potential biomarkers in patients with overt proteinuria.

    Science.gov (United States)

    Jang, Hye Ryoun; Jeon, Junseok; Park, Ji Hyeon; Lee, Jung Eun; Huh, Wooseong; Oh, Ha Young; Kim, Yoon-Goo

    2014-11-01

    Urinary angiotensinogen (AGT) and renin have been reported to reflect the intrarenal renin-angiotensin system (RAS) activity. However, the adequacy and clinical significance of these markers have not been evaluated in overtly proteinuric patients. In patients with biopsy-proven glomerulonephritis, plasma and urinary AGT and renin were analyzed. A cohort of 75 patients treated with RAS inhibitors was followed for 1 year. Among the 207 patients, 105 had subnephrotic and 102 had nephrotic-range proteinuria. Mean age, estimated glomerular filtration rate (eGFR), and urinary protein-to-creatinine ratio (P/Cr) of all patients were 48 years, 79.7 mL/min/1.73 m(2), and 5.66 mg/mg, respectively. Both natural logarithm of urinary AGT/creatinine (ln [urinary AGT/Cr]) and ln (urinary renin/Cr) showed positive correlations with urinary P/Cr. There was a positive correlation between ln (urinary AGT/Cr) and ln (urinary renin/Cr). Ln (urinary renin/Cr) was not affected by ln (plasma renin) regardless of the degree of proteinuria. The treatment response to RAS inhibitors was greatest in patients with high urinary AGT and renin. However, the predictive value of those parameters was no longer present when the values were adjusted by the degree of proteinuria. Ln (urinary renin/Cr) and initial eGFR were independently associated with the changes in renal function for 1 year. Ln (urinary AGT/Cr) was associated with persistent overt proteinuria after 1 year. Our study suggests that urinary renin may be a better marker in heavy proteinuria, and the treatment response to RAS inhibitors may be enhanced in patients with high urinary renin and AGT. Further studies will be necessary to explore the value of urinary AGT and renin.

  12. The 82-plex plasma protein signature that predicts increasing inflammation

    DEFF Research Database (Denmark)

    Tepel, Martin; Beck, Hans C; Tan, Qihua;

    2015-01-01

    transplant recipients and quantified 359 plasma proteins simultaneously using nano-Liquid-Chromatography-Tandem Mass-Spectrometry in individual samples and plasma C-reactive protein on the index day and the next day. Next-day C-reactive protein increased in 59 patients whereas it decreased in 32 patients......The objective of the study was to define the specific plasma protein signature that predicts the increase of the inflammation marker C-reactive protein from index day to next-day using proteome analysis and novel bioinformatics tools. We performed a prospective study of 91 incident kidney....... The prediction model selected and validated 82 plasma proteins which determined increased next-day C-reactive protein (area under receiver-operator-characteristics curve, 0.772; 95% confidence interval, 0.669 to 0.876; P protein signature (P 

  13. Active renin mass concentration to determine aldosterone-to-renin ratio in screening for primary aldosteronism

    OpenAIRE

    Corbin F; Douville P; Lebel M

    2011-01-01

    François Corbin1, Pierre Douville2, Marcel Lebel3 1Division of Biochemistry, l'Université de Sherbrooke, Sherbrooke, Quebec, Canada; 2Division of Biochemistry; 3Division of Nephrology, L'Hôtel-Dieu de Québec Hospital and l'Université Laval, Quebec, CanadaBackground: Active renin mass concentration (ARC) is independent of the endogenous level of angiotensinogen, and less variable and more reproducible than plasma ren...

  14. Renin-angiotensin-aldosterone system and electrolyte metabolism in rat blood after flight aboard Cosmos-1129 biosatellite

    Energy Technology Data Exchange (ETDEWEB)

    Kvetnansky, R.; Tigranyan, R.A.; Jindra, A.; Viting, T.A.

    1982-08-01

    Blood plasma aldosterone concentration and renin activity were studied in rats flow in space on the Cosmos 1129 satellite using radioimmunoassay techniques. Immediately after the flight, the animals presented significant decreases in plasma renin activity, as compared to rats in the vivarium control and animals in the synchronous experiment. R. J.

  15. The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo

    DEFF Research Database (Denmark)

    Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki

    2012-01-01

    Increased cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis have been shown to be prerequisites for renal renin release after Na(+) deprivation. To answer the question of whether EP4 receptor type of PGE(2) mediates renin regulation under a low-salt diet, we examined renin regulation in EP4......(+/+), EP4(-/-), and in wild-type mice treated with EP4 receptor antagonist. After 2 wk of a low-salt diet (0.02% wt/wt NaCl), EP4(+/+) mice showed diminished Na(+) excretion, unchanged K(+) excretion, and reduced Ca(2+) excretion. Diuresis and plasma electrolytes remained unchanged. EP4(-/-) exhibited...... groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced...

  16. Role of cardiopulmonary mechanoreceptors in the postural regulation of renin

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, R.A.; Marco, E.J.; Oliveri, C.; Otero, F.J.; Degrossi, O.; Moledo, L.I.; Julius, S.

    1987-04-01

    To change the stretch on cardiopulmonary mechanoreceptors, large shifts of blood in the capacity space were elicited by tilting and by exerting positive lower body pressure in the tilted position. Twelve volunteers underwent invasive hemodynamic studies and in 10 other subjects cardiac size was determined by radionuclide cardiography. In all 22 subjects tilting caused the expected increase of renin, which was abolished by lower body compression. Decompression caused renin to increase again. Right atrial pressure in invasive studies and end-systolic and end-diastolic counts in noninvasive studies showed a significant and strong negative correlation with renin and norepinephrine levels. Thus, the degree of stretch of the cardiopulmonary mechanoreceptors is a major determinant of reflex regulation of renin release in humans.

  17. The renin-angiotensin system and the central nervous system.

    Science.gov (United States)

    Ganong, W F

    1977-04-01

    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  18. Plasma renin-angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer's disease and show gender differences but are not related to apolipoprotein E genotype.

    Science.gov (United States)

    Puertas, María Del Carmen; Martínez-Martos, José Manuel; Cobo, Manuela; Lorite, Pedro; Sandalio, Rosa María; Palomeque, Teresa; Torres, María Isabel; Carrera-González, María Pilar; Mayas, María Dolores; Ramírez-Expósito, María Jesús

    2013-06-01

    Alterations in blood pressure and components of the renin-angiotensin system (RAS) contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. Aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase N (APN) and aminopeptidase B (APB) catabolise circulating angiotensins, whereas insulin-regulated aminopeptidase (IRAP) has been described as the AT4 receptor. We have found in AD patients a significant decrease of APA activity in men but not in women, and of APN, APB and IRAP in both genders, when compared with control subjects. No changes were found in ASAP activity. Also, APN, APB and IRAP but not APA correlated with the Mini-Mental test, but no relationship with APOE genotype was found. We conclude that several components of the RAS are modified in AD patients, with gender differences. Furthermore, ROC analysis indicates that APN, APB and IRAP activities could be useful non-invasive biomarkers of AD from the earliest stages.

  19. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone

    Science.gov (United States)

    Haber, E.; Re, R. N.; Kourides, I. A.; Weihl, A. C.; Maloof, F.

    1978-01-01

    Prolactin, thyrotropin and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 micrograms of thyrotropin releasing hormone. Prolactin increased at 15 minutes following thyrotropin releasing hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin releasing hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

  20. Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells

    Directory of Open Access Journals (Sweden)

    Andrade A.Q.

    2002-01-01

    Full Text Available Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6 mesangial cells (MC and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05 in the cell lysate (43.5 ± 5.7 ng h-1 10(6 cells than in the culture medium (12.5 ± 2.5 ng h-1 10(6 cells. Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6 cells. Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.

  1. Connexin 43 is not essential for the control of renin synthesis and secretion.

    Science.gov (United States)

    Gerl, Melanie; Kurt, Birgül; Kurtz, Armin; Wagner, Charlotte

    2014-05-01

    The juxtaglomerular areas of mammalian kidneys express the gap junction proteins connexin 37, 40, 43, and 45. Among these, Cx40 plays a major role for the function of juxtaglomerular renin-expressing cells, while Cx37 and Cx45 appear to be less relevant in this context. Since the role of the remaining Cx43 for the function of renin expression is not well understood, this study aimed to systematically characterize the direct role of Cx43 for renin expression and secretion. For this aim, we generated mice with endothelium and with renin cell-specific deletions of Cx43, and we characterized the regulation of renin expression and renin secretion in the kidneys of these mice on normal salt diet and during chronic challenge of the renin system by pretreatment of mice with a low-salt diet in combination with an angiotensin I-converting enzyme inhibitor. We found that renal renin mRNA abundance, plasma renin concentration, and systolic blood pressure did not differ between wild-type, Cx43(fl/fl) Ren1d(+/Cre) mice as well as Cx43(fl/fl) Tie-2(+/Cre) mice under basal conditions nor under chronic stimulation by salt depletion. The localization of renin-expressing cells was also regular in kidneys of all genotypes, and moreover, regulation of renin secretion by beta-adrenergic stimulation and renal perfusion pressure measured in isolated perfused kidneys of Cx43(fl/fl) Ren1d(+/Cre) and Cx43(fl/fl) Tie-2(+/Cre) mice was not different from control. We infer from these results that Cx43 plays if at all only a minor role for the functional control of renin-producing cells in the kidney.

  2. The influence of different sodium loads on renin release in hypertensive and normotensive states of chronic renal failure.

    Science.gov (United States)

    Kornerup, H J

    1978-04-01

    The purpose of the present study was to examine the influence of different sodium loads on renin release in the hypertensive and normotensive state of chronic renal failure. Blood pressure (BP), plasma renin concentration (PRC) and exchangeable sodium (NaE) were measured in eighteen patients with advanced chronic renal failure, nine hypertensives and nine normotensives, and in seven normal subjects (a) 6 days after a fixed sodium intake of 10 mmol/day, and (b) 6 days after a fixed sodium intake of 150 mmol/day. Mean NaE was 14-19% higher in the hypertensives compared with the normotensives and values of NaE correlated significantly to values of mean BP. No significant differences were present in PRC between the groups of patients and controls on either of the sodium regimens and no correlation was found between BP and PRC. However, average decreases of PRC in the hypertensives on high sodium intake, 33-34%, were significantly lower than the corresponding values of 69-71% in the normotensive patients and controls, respectively. Furthermore, the percentage changes of PRC on high sodium intake correlated significantly to mean BP as well as to NaE. These results suggest that renin release is relatively unresponsive to different sodium intakes in hypertension following chronic renal failure. This alteration in renin release may contribute to the maintenance of hypertension in chronic renal failure, PRC being "inappropriately' increased in relationship to the sodium excess.

  3. Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

    Energy Technology Data Exchange (ETDEWEB)

    Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

    1981-10-01

    Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension.

  4. Changes of plasma renin activity and angiotensin Ⅱ level in and its sig-nificance%血浆PRA、AngⅡ在ALI/ARDS患者中的变化和意义

    Institute of Scientific and Technical Information of China (English)

    夏炎火; 郑小蕾; 王丹; 余方友; 林锡芳; 潘景业

    2014-01-01

    目的:探讨PRA、AngⅡ在ALI/ARDS患者中的变化和意义。方法测定ALI/ARDS和非ALI/ARDS患者血浆PRA和AngⅡ浓度,进行APACHEⅡ评分和LIS评分,计算病死率,进一步将患者按预后分组,进行比较和相关分析,利用ROC曲线评价PRA和AngⅡ的诊断分辨度。结果与非ALI/ARDS组相比,ALI/ARDS组血浆PRA和AngⅡ浓度明显增高(P<0.05),死亡组血浆PRA和AngⅡ浓度高于存活组(P <0.05)。 PRA、AngⅡ与APACHEⅡ评分、LIS、乳酸(LAC)间均呈明显正相关。 PRA在预测ALI/ARDS方面有显著意义(AUC=0.705,P=0.001),AngⅡ对预测ALI/ARDS也有显著意义(AUC=0.672, P=0.007)。在预测ALI/ARDS方面,PRA、AngⅡ与LIS相比无明显差异(P=0.923,P=0.713)。结论 ALI/ARDS患者血浆PRA和AngⅡ水平明显升高,两者在预测ALI/ARDS和判断其预后方面均有重要意义,而AngⅡ在预测ALI/ARDS中的特异度较高。%Objective To investigate the clinical significance and levels of plasma renin activity (PRA), Angiotensin (Ang) Ⅱ in ALI / ARDS patients. Methods The levels of PRA and AngⅡ, APACHE Ⅱ score, lung injury score(LIS), and mortality were analyzed in ALI/ARDS patients and non-ALI/ARDS group. After the patients were grouped accord-ing to prognosis, correlation analysis and ROC curve to evaluate diagnostic efficacy of PRA and AngⅡ were performed. Results Compared with non- ALI/ARDS group, the levels of PRA and AngⅡ were significantly increased in ALI/ARDS (P<0.05). In the death group, the levels of PRA and AngⅡwere higher than that of the survival group (P<0.05). It was significant positive correlation between APACHEⅡ score,LIS,lactic acid (LAC) and PRA, so as AngⅡ. In pre-dicting ALI/ARDS, PRA was significant (AUC=0.705, P=0.001), so as AngⅡ(AUC=0.672, P =0.007). In predict-ing ALI/ARDS, there was no significant difference between PRA and LIS (P=0.923), and also between AngⅡ and LIS (P = 0.713). Conclusion

  5. Influential factors on the ratio of plasma aldosterone concentration to plasma renin activity in screening primary aldosteronism%原发性醛固酮增多症筛查中血浆醛固酮/肾素活性比值的影响因素

    Institute of Scientific and Technical Information of China (English)

    鄞国书; 张少玲; 严励; 程桦

    2009-01-01

    The ratio of plasma aldosterone concentration to plasma renin activity (ARR) is a practical parameter in screening for primary aldosteronism (PA).However,variations of the cutoff value of ARR in different studies have been reported due to plenty of influential factors that may affect the secretions of renin and aldosterone. Lack of standardization of assays for ARR also makes direct comparisons among different studies difficult.The associated influential factors on ARR were introduced in this review.%血浆醛固酮水平/肾索活性比值(ARR)是筛查原发性醛固酮增多症的实用指标.由于影响肾素和醛同酮分泌的因素众多,ARR切点值变异范围较大,至今仍然是一个缺乏标准化的指标.本文综述这些因素,旨在临床上提高ARR的诊断效力.

  6. Combined renin inhibition/(pro)renin receptor blockade in diabetic retinopathy--a study in transgenic (mREN2)27 rats.

    Science.gov (United States)

    Batenburg, Wendy W; Verma, Amrisha; Wang, Yunyang; Zhu, Ping; van den Heuvel, Mieke; van Veghel, Richard; Danser, A H Jan; Li, Qiuhong

    2014-01-01

    Dysfunction of renin-angiotensin system (RAS) contributes to the pathogenesis of diabetic retinopathy (DR). Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (pro)renin receptor ((P)RR). Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (P)RR blocker handle-region peptide (HRP) on diabetic retinopathy in streptozotocin (STZ)-induced diabetic transgenic (mRen2)27 rats (a model with high plasma prorenin levels) as well as prorenin stimulated cytokine expression in cultured Müller cells. Adult (mRen2)27 rats were randomly divided into the following groups: (1) non-diabetic; (2) diabetic treated with vehicle; (3) diabetic treated with aliskiren (10 mg/kg per day); and (4) diabetic treated with aliskiren+HRP (1 mg/kg per day). Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen2)27 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen2)27 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Müller cells, prorenin significantly increased the expression levels of IL-1α and TNF-α, and this was completely blocked by aliskiren or HRP, their combination, (P)RR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (P)RR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular

  7. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

    Science.gov (United States)

    Brooks, V. L.; Keil, L. C.

    1992-01-01

    Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

  8. Metabolic control of renin secretion.

    Science.gov (United States)

    Peti-Peterdi, János; Gevorgyan, Haykanush; Lam, Lisa; Riquier-Brison, Anne

    2013-01-01

    One emerging topic in renin-angiotensin system (RAS) research is the direct local control of renin synthesis and release by endogenous metabolic intermediates. During the past few years, our laboratory has characterized the localization and signaling of the novel metabolic receptor GPR91 in the normal and diabetic kidney and established GPR91 as a new, direct link between high glucose and RAS activation in diabetes. GPR91 (also called SUCNR1) binds tricarboxylic acid (TCA) cycle intermediate succinate which can rapidly accumulate in the local tissue environment when energy supply and demand are out of balance. In a variety of physiological and pathological conditions associated with metabolic stress, succinate signaling via GPR91 appears to be an important mediator or modulator of renin secretion. This review summarizes our current knowledge on the control of renin release by molecules of endogenous metabolic pathways with the main focus on succinate/GPR91.

  9. Intrarenal renin-angiotensin system modulates glomerular angiotensin receptors in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Wilkes, B.M.; Pion, I.; Sollott, S.; Michaels, S.; Kiesel, G. (North Shore Univ. Hospital and Cornell Univ. Medical College, Manhasset, NY (USA))

    1988-03-01

    The aim of this study was to test the hypothesis that the intrarenal renin-angiotensin system (RAS) modulates glomerular angiotensin II (ANG II) receptors. In one protocol ANG II receptors were measured 7 days after unilateral denervation of the left kidney in rats. There were 50% more receptors in the glomeruli from denervated compared with innervated kidneys, which was associated with a 63% reduction in left renal vein renin. The differences in ANG II receptors between the left and right kidneys were not longer present when angiotensin-converting enzyme was inhibited with enalapril or when pharmacological amounts of ANG II were infused. In a second protocol, renal cortical renin content was raised in the left kidney by placing a 0.20-mm clip on the left renal artery. At 7 days, glomerular ANG II receptors were reduced by 72.3% in the clipped compared with the contralateral kidneys. The differences in ANG II receptors were no longer present after enalapril treatment. Pharmacological maneuvers that either blocked ANG II formation or increased circulating ANG II resulted in an equal number of ANG II receptors in the right and left kidneys. The data indicate that the intrarenal RAS modulates the density of glomerular ANG II receptors and is a more important receptor modulation than plasma ANG II.

  10. Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease.

    Science.gov (United States)

    Poredos, P; Zizek, B

    1996-03-01

    Increased blood and plasma viscosity has been described in patients with coronary and peripheral arterial disease. However, the relation of viscosity to the extent of arterial wall deterioration--the most important determinant of clinical manifestation and prognosis of the disease--is not well known. Therefore, the authors studied plasma viscosity as one of the major determinants of blood viscosity in patients with different stages of arterial disease of lower limbs (according to Fontaine) and its relation to the presence of some risk factors of atherosclerosis. The study encompassed four groups of subjects: 19 healthy volunteers (group A), 18 patients with intermittent claudication up to 200 m (stage II; group B), 15 patients with critical ischemia of lower limbs (stage III and IV; group C), and 16 patients with recanalization procedures on peripheral arteries. Venous blood samples were collected from an antecubital vein without stasis for the determination of plasma viscosity (with a rotational capillary microviscometer, PAAR), fibrinogen, total cholesterol, alpha-2-macroglobulin, and glucose concentrations. In patients with recanalization procedure local plasma viscosity was also determined from blood samples taken from a vein on the dorsum of the foot. Plasma viscosity was most significantly elevated in the patients with critical ischemia (1.78 mPa.sec) and was significantly higher than in the claudicants (1.68 mPa.sec), and the claudicants also had significantly higher viscosity than the controls (1.58 mPa.sec). In patients in whom a recanalization procedure was performed, no differences in systemic and local plasma viscosity were detected, neither before nor after recanalization of the diseased artery. In all groups plasma viscosity was correlated with fibrinogen concentration (r=0.70, P < 0.01) and total cholesterol concentration (r=0.24, P < 0.05), but in group C (critical ischemia) plasma viscosity was most closely linked to the concentration of alpha-2

  11. Renin Lineage Cells Repopulate the Glomerular Mesangium after Injury

    Science.gov (United States)

    Starke, Charlotte; Betz, Hannah; Hickmann, Linda; Lachmann, Peter; Neubauer, Björn; Kopp, Jeffrey B.; Sequeira-Lopez, Maria Luisa S.; Gomez, R. Ariel; Hohenstein, Bernd; Hugo, Christian P.M.

    2015-01-01

    Mesangial cell injury has a major role in many CKDs. Because renin-positive precursor cells give rise to mesangial cells during nephrogenesis, this study tested the hypothesis that the same phenomenon contributes to glomerular regeneration after murine experimental mesangial injury. Mesangiolysis was induced by administration of an anti-mesangial cell serum in combination with LPS. In enhanced green fluorescent protein–reporter mice with constitutively labeled renin lineage cells, the size of the enhanced green fluorescent protein–positive area in the glomerular tufts increased after mesangial injury. Furthermore, we generated a novel Tet-on inducible triple-transgenic LacZ reporter line that allowed selective labeling of renin cells along renal afferent arterioles of adult mice. Although no intraglomerular LacZ expression was detected in healthy mice, about two-thirds of the glomerular tufts became LacZ positive during the regenerative phase after severe mesangial injury. Intraglomerular renin descendant LacZ-expressing cells colocalized with mesangial cell markers α8-integrin and PDGF receptor-β but not with endothelial, podocyte, or parietal epithelial cell markers. In contrast with LacZ-positive cells in the afferent arterioles, LacZ-positive cells in the glomerular tuft did not express renin. These data demonstrate that extraglomerular renin lineage cells represent a major source of repopulating cells for reconstitution of the intraglomerular mesangium after injury. PMID:24904091

  12. The Renin-Angiotensin System in the Endocrine Pancreas

    Directory of Open Access Journals (Sweden)

    Carlsson PO

    2001-01-01

    Full Text Available Experimental data suggest that a tissue renin-angiotensin system is present in the pancreatic islets of several species, including man. However, the physiological role for this local renin-angiotensin system remains largely unknown. In vitro findings argue against a direct effect of angiotensin II on alpha- and beta-cells. In contrast, when the influence of angiotensin II on the pancreatic islets has been evaluated in the presence of an intact vascular system either in vivo or in the perfused pancreas, a suppression of insulin release has been observed, also in man. These discrepancies may be explained by the profound effects of the renin-angiotensin system on pancreatic islet blood perfusion. Alterations in the systemic renin-angiotensin system and an increased vascular sensitivity for its components have been observed in diabetes mellitus and hypertension. Whether changes occur also in the pancreatic islet renin-angiotensin system during these conditions remains unknown. Future research may help to provide an answer to this question, and to elucidate to what extent the renin-angiotensin system may contribute to beta-cell dysfunction in these diseases.

  13. Increased capillary permeability for plasma proteins in oral contraceptive users.

    Science.gov (United States)

    Tollan, A; Kvenild, K; Strand, H; Oian, P; Maltau, J M

    1992-05-01

    The transcapillary fluid balance was examined in eleven women before administration of a monophasic oral contraceptive (desogestrel 0.15 mg, ethinylestradiol 0.03 mg), and after three and six months of use. The interstitial colloid osmotic pressure was measured by the "wick" method, and the interstitial hydrostatic pressure by the "wick-in-needle" method in subcutaneous tissue on thorax and leg. During the six-month observation period, the following changes were observed: Plasma colloid osmotic pressure decreased (mean 1.8 mmHg, p = 0.047), as well as serum albumin (mean 5.1 g/l, p = 0.0006), total protein concentration (mean 2.8 g/l, p = 0.0006), hemoglobin (mean 0.5 g/dl, p = 0.014) and hematocrit (mean 1.8%, p = 0.047). Blood pressure and body weight remained unchanged, but foot volume showed a significant increase. The colloid osmotic pressure gradient (plasma-interstitium) was significantly reduced. The results indicate an increase in plasma volume in addition to an increased capillary permeability to plasma proteins during oral contraceptive use. We suggest that the observed changes in transcapillary fluid balance is caused by the estrogen component of the oral contraceptive pill.

  14. Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus.

    Science.gov (United States)

    Forhead, Alison J; Jellyman, Juanita K; De Blasio, Miles J; Johnson, Emma; Giussani, Dino A; Broughton Pipkin, Fiona; Fowden, Abigail L

    2015-08-01

    Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10-11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment.

  15. 血浆肾素浓度诊断原发性醛固酮增多症的临床应用%Clinical Application of Plasma Renin Concentration in Diagnosis of Primary Aldosterone

    Institute of Scientific and Technical Information of China (English)

    孟凡森; 王浩

    2015-01-01

    Objective Plasma aldosterone / plasma renin activity (PAC/PRA, ARR) and plasma aldosterone / plasma renin concentration (PAC/PRC, AARR) were used to evaluate the speciifcity and sensitivity of PA (PA) screening.MethodsARR and AARR were measured in 20 patients with essential hypertension and 32 patients with essential hypertension conifrmed by confirmatory test.ResultsThe area under the ROC curve of AARR and ARR was 0.854 and 0.904, respectively, and the area under the AARR curve of ROC and ARR was 0.951 and 0.961 respectively. The sensitivity and speciifcity of ARR were 78% and 80% when cutoff value was 70.5, the sensitivity and specificity of ARR was 80% and 100% respectively. The sensitivity and specificity of AARR were 93.3% and 80.65, respectively. The sensitivity and speciifcity of AARR were 100% and 87.8% respectively. The diagnostic value of AARR and ARR was similar to that of, and it had a higher accuracy, and the value of AARR was higher than that of ARR. Conclusion The accuracy of AARR and ARR in PA screening is quite, and the AARR method is more simple than ARR.%目的:比较应用血浆醛固酮/血浆肾素活性(PAC/PRA,ARR)及血浆醛固酮/血浆肾素浓度(PAC/PRC,AARR)进行原发性醛固酮增多症(PA)筛查的特异性和敏感性差异,评价测定血浆肾素浓度在PA筛查中的价值。方法对20例经确证实验证实的原发性醛固酮患者和32例经筛查诊断为原发性高血压的患者测定ARR与AARR。结果 AARR和ARR卧位的ROC曲线下面积分别为0.904和0.854, AARR和ARR立位的ROC曲线下面积分别为0.951和0.961。ARR卧位cutoff值在70.5时,诊断原醛的敏感性和特异性分别为80%和78%;ARR立位cutoff值在78时,诊断原醛的敏感性和特异性分别为80%和100%;AARR卧位cutoff值在80.65时,诊断原醛的敏感性和特异性分别为93.3%和75.6%;AARR立位cutoff值在44.65时,诊断原醛的敏感性和特异性分别为100%和87.8%。AARR立位与ARR

  16. Normotensive sodium loading in conscious dogs: Regulation of renin secretion during beta receptor blockade

    DEFF Research Database (Denmark)

    Bie, Peter; Mølstrøm, Simon; Wamberg, Søren

    2009-01-01

    irrespective of diet. In conclusion, PRC depended on dietary sodium and beta1-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by beta1-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or beta1......Renin secretion is regulated in part by renal nerves operating through beta1-receptors of the renal juxtaglomerular cells. Slow sodium loading may decrease plasma renin (PRC) and cause natriuresis at constant mean arterial blood pressure (MAP) and glomerular filtration rate (GFR). We hypothesized...... that in this setting, renin secretion and renin-dependent sodium excretion are controlled by via the renal nerves and therefore eliminated or reduced by blocking the action of norepinephrine on the juxtaglomerular cells with the beta1-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of Na...

  17. Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension.

    Science.gov (United States)

    Ramkumar, Nirupama; Stuart, Deborah; Rees, Sara; Hoek, Alfred Van; Sigmund, Curt D; Kohan, Donald E

    2014-10-15

    The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP and renal salt and water excretion. Mice containing loxP-flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin-2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal-Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400 ng·kg(-1)·min(-1) resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 ± 4 mmHg in KO vs. 128 ± 3 mmHg in controls). Urinary renin excretion and epithelial Na(+) channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane-associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression.

  18. Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible?

    Science.gov (United States)

    Emdin, Michele; Fatini, Cinzia; Mirizzi, Gianluca; Poletti, Roberta; Borrelli, Chiara; Prontera, Concetta; Latini, Roberto; Passino, Claudio; Clerico, Aldo; Vergaro, Giuseppe

    2015-03-30

    Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of

  19. The functional c.-2G>C variant of the mineralocorticoid receptor modulates blood pressure, renin, and aldosterone levels.

    Science.gov (United States)

    van Leeuwen, Nienke; Caprio, Massimiliano; Blaya, Carolina; Fumeron, Frédéric; Sartorato, Paola; Ronconi, Vanessa; Giacchetti, Gilberta; Mantero, Franco; Fernandes-Rosa, Fabio L; Simian, Christophe; Peyrard, Sévrine; Zitman, Frans G; Penninx, Brenda W J H; de Kloet, E Ron; Azizi, Michel; Jeunemaitre, Xavier; Derijk, Roel H; Zennaro, Maria-Christina

    2010-11-01

    The mineralocorticoid receptor (MR) is essential in the regulation of volemia and blood pressure. Rare mutations in the MR gene cause type 1 pseudohypoaldosteronism and hypertension. In this study we characterized the common MR polymorphism c.-2G>C (rs2070951) in vitro and tested its influence on parameters related to blood pressure regulation and the renin-angiotensin system. In vitro studies showed that the G allele was associated with decreased MR protein levels and reduced transcriptional activation compared with the C allele. Association studies were performed with several outcome variables in 3 independent cohorts: a mild hypertensive group subjected to a salt-sensitivity test, a healthy normotensive group included in a crossover study to receive both a high and low Na/K diet, and a large cohort (The Netherlands Study of Depression and Anxiety), in which blood pressure was measured. Subjects with the GG genotype had significantly higher plasma renin levels both in the mild hypertensive group and in normal volunteers compared with homozygous C carriers. The GG genotype was also correlated with higher plasma aldosterone levels in healthy subjects. In both the mild hypertensive group and The Netherlands Study of Depression and Anxiety cohort the genotype GG was associated with higher systolic blood pressure in males. In conclusion, the G allele of the common functional genetic polymorphism c.-2G>C in the MR gene associates with increased activation of the renin-angiotensin-aldosterone axis and with increased blood pressure, probably related to decreased MR expression.

  20. Autophagy and the (Pro)renin Receptor.

    Science.gov (United States)

    Binger, Katrina J; Muller, Dominik N

    2013-10-21

    The (pro)renin receptor (PRR) is a newly reported member of the renin-angiotensin system (RAS); a hormonal cascade responsible for regulating blood pressure. Originally, identification of PRR was heralded as the next drug target of the RAS, of which such therapies would have increased benefits against target-organ damage and hypertension. However, in the years since its discovery, several conditional knockout mouse models of PRR have demonstrated an essential role for this receptor unrelated to the RAS and blood pressure. Specific deletion of PRR in podocytes or cardiomyocytes resulted in the rapid onset of organ failure and subsequently animal mortality after only a matter of weeks. In both cell types, loss of PRR resulted in the intracellular accumulation of autophagosomes and misfolded proteins, indicating a disturbance in autophagy. In light of the fact that the majority of PRR is located intracellularly, this molecular function appears to be more relevant than its ability to bind to high, non-physiological concentrations of (pro)renin. This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis. Understanding the link between PRR, autophagy and how its loss results in cell death will be essential for deciphering its role in physiology and pathology.

  1. Plasma alpha(2) macroglobulin is increased in nephrotic patients as a result of increased synthesis alone

    NARCIS (Netherlands)

    Sain-van der Velden, MGM; Rabelink, TJ; Reijngoud, DJ; Gadellaa, MM; Voorbij, HAM; Stellaard, F; Kaysen, GA

    1998-01-01

    Background. alpha(2) Macroglobulin (alpha(2)M), a protease inhibitor, is often increased in plasma of patients with the nephrotic syndrome. Although it has been speculated that synthesis is increased, no direct measurements have been performed. Methods. alpha(2)M synthesis in both normal subjects (N

  2. The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-I levels

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

    2006-01-01

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-I levels in a large population-based sample from the PR

  3. Betaine increases the butyrylcholinesterase activity in rat plasma.

    Science.gov (United States)

    Šišková, K; Dubničková, M; Pašková, Ľ; Rajdl, D; Ďuračková, Z; Muchová, J; Pauliková, I; Racek, J

    2016-01-01

    The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; pbetaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account.

  4. Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension.

    Science.gov (United States)

    Moniwa, Norihito; Varagic, Jasmina; Ahmad, Sarfaraz; VonCannon, Jessica L; Simington, Stephen W; Wang, Hao; Groban, Leanne; Brosnihan, K Bridget; Nagata, Sayaka; Kato, Johji; Kitamura, Kazuo; Gomez, R Ariel; Lopez, Maria L Sequeira; Ferrario, Carlos M

    2013-02-01

    We examined the antihypertensive effects of valsartan, aliskiren, or both drugs combined on circulating, cardiac, and renal components of the renin-angiotensin system in congenic mRen2.Lewis hypertensive rats assigned to: vehicle (n=9), valsartan (via drinking water, 30 mg/kg per day; n=10), aliskiren (SC by osmotic mini-pumps, 50 mg/kg per day; n=10), or valsartan (30 mg/kg per day) combined with aliskiren (50 mg/kg per day; n=10). Arterial pressure and heart rate were measured by telemetry before and during 2 weeks of treatment; trunk blood, heart, urine, and kidneys were collected for measures of renin-angiotensin system components. Arterial pressure and left-ventricular weight/tibia length ratio were reduced by monotherapy of valsartan, aliskiren, and further reduced by the combination therapy. Urinary protein excretion was reduced by valsartan and further reduced by the combination. The increases in plasma angiotensin (Ang) II induced by valsartan were reversed by the treatment of aliskiren and partially suppressed by the combination. The decreases in plasma Ang-(1-7) induced by aliskiren recovered in the combination group. Kidney Ang-(1-12) was increased by the combination therapy whereas the increases in urinary creatinine mediated by valsartan were reversed by addition of aliskiren. The antihypertensive and antiproteinuric actions of the combined therapy were associated with marked worsening of renal parenchymal disease and increased peritubular fibrosis. The data show that despite improvements in the surrogate end points of blood pressure, ventricular mass, and proteinuria, dual blockade of Ang II receptors and renin activity is accompanied by worsening of renal parenchymal disease reflecting a renal homeostatic stress response attributable to loss of tubuloglomerular feedback by Ang II.

  5. Wheat aleurone polyphenols increase plasma eicosapentaenoic acid in rats

    Directory of Open Access Journals (Sweden)

    Fayçal Ounnas

    2014-08-01

    Full Text Available Methods: These studies were designed to assess whether wheat polyphenols (mainly ferulic acid [FA] increased the very-long-chain omega-3 fatty acids (VLC n-3 [eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA] in rats. Wheat aleurone (WA was used as a dietary source of wheat polyphenols. Two experiments were performed; in the first one, the rats were fed WA or control pellets (CP in presence of linseed oil (LO to provide alpha-linolenic acid (ALA, the precursor of VLC n-3. In the second one, the rats were fed WA or CP in presence of control oil (CO without ALA. The concentrations of phenolic acid metabolites in urine were also investigated. Results: The urinary concentration of conjugated FA increased with WA ingestion (p<0.05. Plasma EPA increased by 25% (p<0.05 with WA in the CO group but not in the LO group. In contrast, there was no effect of WA on plasma DHA and omega-6 fatty acids (n-6. Finally, both n-3 and n-6 in the liver remained unchanged by the WA. Conclusion: These results suggest that WA consumption has a significant effect on EPA in plasma without affecting n-6. Subsequent studies are required to examine whether these effects may explain partly the health benefits associated with whole wheat consumption.

  6. Identification of ATF2 as a transcriptional regulator of renin gene.

    Science.gov (United States)

    Desch, Michael; Hackmayer, Gerit; Todorov, Vladimir T

    2012-01-01

    The cAMP response element (enhCRE) in the distal enhancer regulatory region of renin gene is believed to play a major role in the control of renin transcription. enhCRE binds the CRE-binding protein (CREB), which is the main transcription factor target of cAMP signaling. Using the mouse renin-producing cell line As4.1 we found that activating transcription factor-2 (ATF2) also binds to enhCRE. N-terminal phosphorylation of ATF2, which controls its transactivation, is associated with downregulation of renin gene expression by the cytokine tumor necrosis factor-α (TNFα). The ubiquitin proteasome inhibitor MG132 also phosphorylates ATF2 and inhibits renin expression. Knockdown of ATF2 attenuated the suppression of renin gene expression by MG132, thus demonstrating that ATF2 mediates the inhibitory effect of MG132. In addition, MG132 increased the DNA-binding of ATF2 as well as the ratio of bound ATF2 to CREB. Using ATF2- and CREB-Gal4 fusion protein constructs coupled with luciferase reporter system we showed that ATF2 has a weaker transactivating capacity than CREB. These data suggest that ATF2 represses renin expression by drifting the transcriptional control of renin gene away from CREB. Accordingly, TNFα completely abrogated the cAMP-dependent stimulation of renin gene expression.

  7. Plasma resistin is increased in patients with unstable angina

    Institute of Scientific and Technical Information of China (English)

    HU Wen-lan; QIAO Shu-bin; HOU Qing; YUAN Jian-song

    2007-01-01

    Background Resistin, a novel adipokine linked to insulin resistance and obesity in rodents, which is derived mainly from macrophages and identified in atheromas in human, has been shown to play a potential role in atherosclerosis.Resistin levels were reported to increase in coronary artery disease (CAD), while data concerning resistin in different stages of CAD in Chinese people are lacking. The aim of this study was to assess whether plasma concentrations of resistin differed between patients with unstable and stable angina pectoris.Methods Plasma resistin levels were determined by means of enzyme-linked immunosorbent assay (ELISA) in 46 patients with unstable angina (UAP), 37 with stable angina (SAP) and 31 control subjects.Results Plasma concentrations of resistin were significantly increased in UAP group (geometric mean (interquartile range) 12.09 ng/ml (8.40, 18.08)) in comparison with SAP (9.04 ng/ml (7.09, 11.44)) and control groups (8.71 ng/ml (6.58,11.56)). No differences in resistin levels were found between patients with SAP and controls. We also found that plasma resistin positively correlated with leukocyte counts (r=0.21, P=0.027), high sensitive C-reactive protein (hs-CRP) (r=0.25,P=0.008), and endothelin-1 (r=0.21, P=0.025) after adjustment for age, sex and BMI.Conclusion Resistin may be involved in the development of CAD by influencing systemic inflammation and endothelial activation.

  8. Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone. Summary report, 1 February 1977--31 January 1978

    Energy Technology Data Exchange (ETDEWEB)

    Haber, E.; Re, R.N.; Kourides, I.A.; Weihl, A.C.; Maloof, F.

    1978-01-31

    Prolactin, thyrotropin, and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 ..mu..g of thyrotropin-releasing-hormone. Prolactin increased at 15 min following injection of thyrotropin-releasing-hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin-releasing-hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin-releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

  9. A study of temperature effect on the activity of plasma angiotensinⅡ and renin%温度对血管紧张素Ⅱ及肾素活性结果影响的研究

    Institute of Scientific and Technical Information of China (English)

    姚一帆

    2013-01-01

    Objective To study the concentration changes of plasma angiotensinⅡ(AⅡ) and renin activity (PRA) in different temperature conditions. Methods Ninety blood samples were collected from 30 patients and divided into 3 groups. In the first group, the procedure followed the handling protocol provided by the manufacturers for the AⅡand PRA kits precisely. The other two groups kept at room temperature and 40C for 2 hours respectively, and then processed samples by the handling protocol the first group followed. In addition, other 20 specimens were separately stored for 1, 2, 3, 7 and 14 days at 4°C and -20°C to evalu-ate the stability of AⅡand PRA. Results When blood samples were kept at room temperature for 2 hours, the PRA and AⅡde-creased significantly (P0.05),在4℃环境中,AⅡ与PRA前3天结果没有显著性差异,P>0.05。3天到14天有显著性差异,P0.05。 PRA在7天内的结果无统计学差异,P>0.05。而7天到14天有显著性差异,P<0.05。结论 AⅡ和PRA对温度敏感,室温放置能使其结果偏低,而在低温环境中能够保持结果稳定。建议AⅡ和PRA标本的运送与预处理都应该在低温中进行,并制定详细的操作规程确保在日常工作中流程的可靠。

  10. The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suyeon [University of Tennessee, Knoxville (UTK); Soltani-Bejnood, Morvarid [University of Tennessee, Knoxville (UTK); Quignard-Boulange, Annie [Centre Biomedical des Cordeliers, Paris, France; Massiera, Florence [Centre de Biochimie, Nice, France; Teboul, Michele [Centre de Biochimie, Nice, France; Ailhaud, Gerard [Centre de Biochimie, Nice, France; Kim, Jung [University of Tennessee, Knoxville (UTK); Moustaid-Moussa, Naima [University of Tennessee, Knoxville (UTK); Voy, Brynn H [ORNL

    2006-07-01

    BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO), and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

  11. New monoclonal antibodies directed against human renin. Powerful tools for the investigation of the renin system.

    OpenAIRE

    Galen, F X; Devaux, C.; Atlas, S; Guyenne, T; Menard, J; Corvol, P; Simon, D.; Cazaubon, C; Richer, P; Badouaille, G

    1984-01-01

    Monoclonal antibodies directed against human renin were obtained by the fusing of myeloma cells with spleen cells from Balb/c or high-responder Biozzi mice injected with pure tumoral or highly purified renal renin. These procedures resulted in the production of seven stable monoclonal antibodies to human renin. Antibodies in the hybridoma culture medium were screened by binding to pure iodinated renin or insolubilized renin in a solid phase assay. The concentration of purified antibodies that...

  12. Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

    Science.gov (United States)

    Weir, Matthew R; Bakris, George L; Gross, Coleman; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Yuan, Jinwei; Berman, Lance; Williams, Gordon H

    2016-09-01

    Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

  13. Multiple short-term effects of lead on the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Goldman, J.M.; Vander, A.J.; Mouw, D.R.; Keiser, J.; Nicholls, M.G.

    1981-02-01

    We previously demonstrated that lead (3 mg/kg iv) sharply raises PRA in dogs. In the present study, the short-term effects of the same dose of lead on renin secretion, hepatic removal of renin, and arterial All levels were measured in anesthetized dogs. Despite large increases in PRA in all nine lead-treated dogs, renin secretion increased in only three out of nine lead-treated animals (those whith the lowest baseline renin secretion). Hepatic extraction of renin was eliminated by lead, and so total hepatic removal of renin became zero by 2 or 3 hr after lead administration. Finally, despite large increases in PRA, All levels did not rise after lead. The linear relationship of All to PRA seen in animals not treated with lead was changed, so that after lead, All levels were disproportionately low for the corresponding level of PRA. It is concluded that lead may increase renin secretion in animals otherwise unstimulated to secrete but that the major mechanism for the short-term rise in PRA after lead is elimination of hepatic removal of renin; further, lead prevents All from rising proportionately with PRA, presumably by inhibiting angiotensin-converting enzyme.

  14. 钠负荷及依那普利对肾积水小鼠肾素合成与分泌的相互作用%Interaction of sodium loading and enalapril on renin mRNA and renin release in hydronephrotic mice

    Institute of Scientific and Technical Information of China (English)

    张延玲; 武俊艳; 王学春; 刘磊

    2009-01-01

    本文应用肾积水小鼠,探讨了钠负荷及依那普利(enalapril)对.肾素合成及分泌的相互作用.实验动物分为4组:假手术组、钠负荷组、依那普利组、钠负荷及依那普利联合组.Balb/C小鼠采用左侧输尿管结扎形成肾积水.在不同的条件下,对主动脉及双侧肾静脉的血浆肾素浓度(plasma renin concentration,PRC)、肾组织肾素浓度(tissue renin concentration,TRC)及肾素mRNA水平进行了测定.与假手术组相比,钠负荷小鼠中,双侧肾静脉PRC降低(P<0.05),肾积水一侧的TRC及肾素mRNA也显著降低(P<0.05).用依那普利治疗肾积水小鼠后,PRC、双侧TRC及肾素mRNA水平高于假手术组(P<0.01).应用钠负荷及依那普利联合治疗,其效应较单独应用依那普利时为低,肾积水一侧肾静脉PRC与主动脉内PRC相似.以上结果提示,在正常及肾积水肾脏,钠负荷与依那普利通过相互作用而影响肾素-血管紧张素系统(renin-angiotensin system,RAS).肾素合成的调节可独立于致密斑,但后者对肾素分泌起重要调节作用.%The present study investigated the interaction between sodium loading and enalapril on renin synthesis and secretion in hydronephrotic mice. Four different experimental groups (n=10 each) were used: sham-operated animals with normal diet (controlgroup); sodium loading (SL group); enalapril treatment with normal diet (E group), or sodium loading combined with enalapril treatment (SL+E group). The hydronephrotic left kidney was induced by unilateral ureteral ligation in mice in the latter three groups. Plasma renin concentration (PRC) in the aorta, both the left and right renal veins, tissue renin concentration (TRC) and renin mRNA levels in the kidneys were examined under different procedures. In hydronephrotic mice treated with sodium loading, PRC in the left and right renal veins was lower than that in control mice (P<0.05), and TRC and renin mRNA levels in the hydronephrotic kidney were also

  15. Weight reduction is associated with increased plasma fibrin clot lysis.

    Science.gov (United States)

    Brzezińska-Kolarz, Beata; Kolarz, Marek; Wałach, Angelika; Undas, Anetta

    2014-11-01

    Obesity is associated with an increased risk of vascular thrombotic events. We sought to investigate how obesity and weight loss affect plasma fibrin clot properties. A total of 29 obese patients were studied before and after 3-month low-fat diet. Plasma fibrin clot parameters, including fibrin clot permeation coefficient (Ks), the lag phase of the turbidity curve, clot lysis time (t 50%), maximum rate of increase in D-dimer levels, and maximum D-dimer concentrations, were determined. Low-fat diet resulted in the reduction of body weight (P < .0001), body mass index (P < .0001), fat mass (P < .0001), total cholesterol (P < .0001), low-density lipoprotein cholesterol (P = .0005), triglycerides (P = .008), and plasminogen activator inhibitor 1 (P = .02), but not in fibrinogen or C-reactive protein. The only change in fibrin clot variables was shorter t 50% (P = .02). Baseline t 50%, but not posttreatment, correlated with waist circumference (r = .44, p = .02). This study demonstrates that weight loss in obese people can increase the efficiency of fibrin clot lysis.

  16. Tetracyclines increase lipid phosphate phosphatase expression on plasma membranes and turnover of plasma lysophosphatidate.

    Science.gov (United States)

    Tang, Xiaoyun; Zhao, Yuan Y; Dewald, Jay; Curtis, Jonathan M; Brindley, David N

    2016-04-01

    Extracellular lysophosphatidate and sphingosine 1-phosphate (S1P) are important bioactive lipids, which signal through G-protein-coupled receptors to stimulate cell growth and survival. The lysophosphatidate and S1P signals are terminated partly by degradation through three broad-specificity lipid phosphate phosphatases (LPPs) on the cell surface. Significantly, the expression of LPP1 and LPP3 is decreased in many cancers, and this increases the impact of lysophosphatidate and S1P signaling. However, relatively little is known about the physiological or pharmacological regulation of the expression of the different LPPs. We now show that treating several malignant and nonmalignant cell lines with 1 μg/ml tetracycline, doxycycline, or minocycline significantly increased the extracellular degradation of lysophosphatidate. S1P degradation was also increased in cells that expressed high LPP3 activity. These results depended on an increase in the stabilities of the three LPPs and increased expression on the plasma membrane. We tested the physiological significance of these results and showed that treating rats with doxycycline accelerated the clearance of lysophosphatidate, but not S1P, from the circulation. However, administering 100 mg/kg/day doxycycline to mice decreased plasma concentrations of lysophosphatidate and S1P. This study demonstrates a completely new property of tetracyclines in increasing the plasma membrane expression of the LPPs.

  17. Association of Free Radicals and the Tissue Renin-Angiotensin System: Prospective Effects of Rhodiola, a Genus of Chinese Herb, on Hypoxia-Induced Pancreatic Injury

    OpenAIRE

    2001-01-01

    The renin-angiotensin system has long been recognized as crucial factor in the regulation of the systemic blood pressure and renal electrolyte homeostasis. Numerous studies have demonstrated the presence of a local renin-angiotensin system in a variety of organs. A recent study of the pancreatic renin-angiotensin system showed that chronic hypoxia significantly increased the mRNA expression for angiotensinogen II receptor subtypes AT1b and AT2. The activation of the renin-angiotensin system m...

  18. The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Suyeon Kim

    2006-01-01

    Full Text Available Background. The adipose tissue renin-angiotensin system (RAS contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results. A panel of mouse models including mice lacking angiotensinogen, Agt (Agt-KO, mice expressing Agt solely in adipose tissue (aP2-Agt/Agt-KO, and mice overexpressing Agt in adipose tissue (aP2-Agt was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. aP2-Agt mice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2-Agt mice. Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

  19. PPARgamma-dependent regulation of adenylate cyclase 6 amplifies the stimulatory effect of cAMP on renin gene expression.

    Science.gov (United States)

    Desch, Michael; Schubert, Thomas; Schreiber, Andrea; Mayer, Sandra; Friedrich, Björn; Artunc, Ferruh; Todorov, Vladimir T

    2010-11-01

    The second messenger cAMP plays an important role in the regulation of renin gene expression. Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is known to stimulate renin gene transcription acting through PPARγ-binding sequences in renin promoter. We show now that activation of PPARγ by unsaturated fatty acids or thiazolidinediones drastically augments the cAMP-dependent increase of renin mRNA in the human renin-producing cell line Calu-6. The underlying mechanism involves potentiation of agonist-induced cAMP increase and up-regulation of adenylate cyclase 6 (AC6) gene expression. We identified a palindromic element with a 3-bp spacer (Pal3) in AC6 intron 1 (AC6Pal3). AC6Pal3 bound PPARγ and mediated trans-activation by PPARγ agonist. AC6 knockdown decreased basal renin mRNA level and attenuated the maximal PPARγ-dependent stimulation of the cAMP-induced renin gene expression. AC6Pal3 decoy oligonucleotide abrogated the PPARγ-dependent potentiation of cAMP-induced renin gene expression. Treatment of mice with PPARγ agonist increased AC6 mRNA kidney levels. Our data suggest that in addition to its direct effect on renin gene transcription, PPARγ "sensitizes" renin gene to cAMP via trans-activation of AC6 gene. AC6 has been identified as PPARγ target gene with a functional Pal3 sequence.

  20. 高血压病患者的血浆肾素活性与脑钠肽水平及预后的关系%Relationship between plasma renin activity,brain natriuretic peptide level,and prognosis in patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    马军; 蒋金法

    2014-01-01

    Objective To observe the difference of brain natriuretic peptide(BNP)level in hypertensive patients with various plasma renin activity,and to follow up the clinical outcome within 12 months. Methods Eight hundred and forty-five cases of new hypertensive patients as the research object. The patients on the same risk level were divided into high renin and low renin groups according by five points,the difference of BNP level between the two groups was compared,and cardiovascular events were followed up for 12 months. Results In low or moderate risk-patients with high blood pressure,plasma renin level difference had little impact on BNP concentration and clinical events. The differences of the renin activity among high-risk patients had a significant influence only on BNP level. The plasma BNP level and cardiovascular events (myocardial infarction,unstable angina,sudden cardiac death,heart failure,malignant arrhythmia,stroke) in high-rennin group were significantly higher than those in low-renin group. Conclusion Extremely high-risk hypertensive patients with high renin activity had higher BNP levels,which might participate in the target organ damage from hypertension,leading to more cardiovascular events.%目的:观察具有不同血浆肾素活性的高血压病患者中血清脑钠肽(BNP)水平的差异,并随访12个月内的临床转归情况。方法将845例新发高血压病患者作为研究对象,对同一危险分层的患者根据血浆肾素差异按5分位法分取高肾素组和低肾素组,比较两组血清BNP水平的差异,并随访12个月内心脑血管事件的发生情况。结果低、中危高血压患者中血清肾素水平差异对血浆BNP水平和临床事件的影响甚微;高危患者中肾素活性的差异仅对BNP的影响具有显著性;极高危患者的高肾素组,其血浆BNP浓度和心脑血管事件(心肌梗死、不稳定型心绞痛、心源性猝死、心力衰竭、恶性心律失常、脑卒中)

  1. Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ferenc Szalay; Mónika B Hantos; Andrea Horvath; Peter L. Lakatos; Aniko Folhoffer; Kinga Dunkel; Dalma Hegedus; Kornélia Tekes

    2004-01-01

    AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor.It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain,and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma.METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor.Hepatocellular carcinoma was diagnosed by laboratory,ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases.RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0±2.7 pg/mL, n=26),primary biliary cirrhosis (12.1±3.2 pg/mL, n=21) and liver cirrhosis (12.8±4.0 pg/mL, n=15) compared to the healthy controls (9.2±1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found (105.9±14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9±14.9 pg/mL, n=12) and without (107.7±14.5pg/mL, n=6).CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.

  2. Biphenyl/diphenyl ether renin inhibitors: filling the S1 pocket of renin via the S3 pocket.

    Science.gov (United States)

    Yuan, Jing; Simpson, Robert D; Zhao, Wei; Tice, Colin M; Xu, Zhenrong; Cacatian, Salvacion; Jia, Lanqi; Flaherty, Patrick T; Guo, Joan; Ishchenko, Alexey; Wu, Zhongren; McKeever, Brian M; Scott, Boyd B; Bukhtiyarov, Yuri; Berbaum, Jennifer; Panemangalore, Reshma; Bentley, Ross; Doe, Christopher P; Harrison, Richard K; McGeehan, Gerard M; Singh, Suresh B; Dillard, Lawrence W; Baldwin, John J; Claremon, David A

    2011-08-15

    Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension.

  3. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

    Science.gov (United States)

    Jacob, G.; Robertson, D.; Mosqueda-Garcia, R.; Ertl, A. C.; Robertson, R. M.; Biaggioni, I.

    1997-01-01

    PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

  4. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

    Science.gov (United States)

    Jacob, G.; Robertson, D.; Mosqueda-Garcia, R.; Ertl, A. C.; Robertson, R. M.; Biaggioni, I.

    1997-01-01

    PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

  5. 不同术后镇痛方法对血浆肾素-血管紧张素Ⅱ-醛固酮系统的影响%Influence of postoperative analgesic method on plasma renin-angiotensin-aldosterone system in patients undergoing hysterectomy

    Institute of Scientific and Technical Information of China (English)

    余微萍; 徐旭仲; 温怀凯; 寿红艳

    2001-01-01

    目的:观察不同术后镇痛方法对子宫切除术患者血浆肾素-血管紧张素-醛固酮(R-A-A)系统的影响。方法: 将36例ASAⅠ~Ⅱ级子宫切除术患者,随机分为持续硬膜外输注镇痛(CEA)组、持续静脉输注镇痛(CIA)组和哌替啶肌注镇痛(MA)组,每组12例。分别于麻醉前(T0)、术毕使用镇痛药前(T1)、术后4小时(T2)和术后第一天晨7时(T3)采静脉血测定血浆肾素、血管紧张素Ⅱ和醛固酮浓度。结果: 与T0比较,肾素水平CEA组、CIA组在T3升高,MA组在T2显著降低(P<0.01);血管紧张素ⅡCEA组在T2、T3和MA组在T3均显著降低(P<0.01);醛固酮CEA组在T3显著降低(P<0.01),MA组在T2升高(P<0.01),而T3时降低(P<0.01)。组间比较,CEA组、MA组在T2和T3时肾素、血管紧张素Ⅱ、在T3时醛固酮浓度显著低于CIA组(P小于0.05或 0.01)。结论:CIA患者R-A-A系统较稳定,CEA患者R-A-A系统被抑制。%Objective:To study the effects of postoperative analgesia on plasma renin-angiotensin-aldosterone(R-A-A)system in patients undergoing hysterectomy.Methods:Thirty-six patients,ASA gradeⅠ~Ⅱ,scheduled for elective hysterectomy ,were randomly divided into continuous epidural analgesia(CEA),continuous introvenous analgesia(CIA) and traditional meperidine intramuscular analgesia(MA) groups. Plasma renin,angiotensin and aldosterone concentrations were measured before anesthesia(T0),operation over and before analgesia(T1),4h after operation(T2),and 7o'clock of next day after surgery.Results:Compared with T0 ,renin levels at T3 were significantly higher in CEA and CIA groups (P<0.05),but in MA group, it was markedly low at T2 (P<0.01),Angiotensin concentrations at T2 and T3 were significantly low in CEA group(P<0.01),and significantly low at T3 in MA group(P<0.01),aldosterone constrations increased significantly in three groups at T1(P<0.05 or 0.01),but decreased markedly at T3 in CEA group

  6. Renin, (pro)renin and receptor: an update.

    Science.gov (United States)

    Nguyen, Genevieve

    2011-03-01

    PRR [(pro)renin receptor] was named after its biological characteristics, namely the binding of renin and of its inactive precursor prorenin, that triggers intracellular signalling involving ERK (extracellular-signal-regulated kinase) 1/2. However the gene encoding for PRR is named ATP6ap2 (ATPase 6 accessory protein 2) because PRR was initially found as a truncated form co-purifying with V-ATPase (vacuolar H+-ATPase). There are now data showing that this interaction is not only physical, but also functional in the kidney and the heart. However, the newest and most fascinating development of PRR is its involvement in both the canonical Wnt/β-catenin and non-canonical Wnt/PCP (planar cell polarity) pathways, which are essential for adult and embryonic stem cell biology, embryonic development and disease, including cancer. In the Wnt/β-catenin pathway, it has been shown that PRR acts as an adaptor between the Wnt receptor LRP5/6 (low-density lipoprotein receptor-related protein 5/6) and Fz (frizzled) and that the proton gradient generated by the V-ATPase in endosomes is necessary for LRP5/6 phosphorylation and β-catenin activation. In the Wnt/PCP pathway, PRR binds to Fz and controls its asymetrical subcellular distribution and therefore the polarization of the cells in a plane of a tissue. These essential cellular functions of PRR are independent of renin and open new avenues on the pathophysiological role of PRR. The present review will summarize our knowledge of (pro)renin-dependent functions of PRR and will discuss the newly recognized functions of PRR related to the V-ATPase and to Wnt signalling.

  7. Atazanavir increases the plasma concentrations of 1200 mg raltegravir dose.

    Science.gov (United States)

    Krishna, Rajesh; East, Lilly; Larson, Patrick; Valiathan, Chandni; Deschamps, Kathleen; Luk, Julie Ann; Bethel-Brown, Crystal; Manthos, Helen; Brejda, John; Gartner, Michael

    2016-12-01

    Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.). Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non-inferior to the marketed 400 mg b.i.d. dose at 48 weeks in a phase 3 trial. Since raltegravir is eliminated mainly by metabolism via a uridine diphosphate glucuronosyltransferase (UGT) 1A1-mediated glucuronidation pathway, co-administration of UGT1A1 inhibitors may increase the plasma levels of q.d. RAL. To assess this potential, the drug interaction of 1200 mg raltegravir using atazanavir, a known UGT1A1 inhibitor, was studied. An open-label, randomized, 2-period, fixed-sequence phase 1 study was performed in adult healthy male and female (non-childbearing potential) subjects ≥ 19 and ≤ 55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m(2) . Subjects (n = 14) received a single oral dose of 1200 mg raltegravir in period 1. After a washout period of at least 7 days, the subjects received oral doses of 400 mg atazanavir q.d. for 9 consecutive days, with a single oral dose of 1200 mg raltegravir co-administered on day 7 of period 2. Serial blood samples were collected for 72 h following raltegravir dosing and analysed using a validated bioanalytical method to quantify raltegravir plasma concentrations. Co-administration with atazanavir yielded GMRs (90% CIs) for raltegravir AUC0-∞ , Cmax and C24 of 1.67 (1.34, 2.10), 1.16 (1.01, 1.33) and 1.26 (1.08, 1.46), respectively. There was no effect of raltegravir on serum total bilirubin. In contrast, atazanavir increased the mean bilirubin by up to 200%, an effect that was preserved in the atazanavir/raltegravir treatment group. Administration of single q.d. RAL alone and co-administered with multiple oral doses of atazanavir were generally well tolerated in healthy subjects. The results show that

  8. Reproduction and the renin-angiotensin system.

    Science.gov (United States)

    Ganong, W F

    1995-01-01

    A unique aspect of the circulating renin-angiotensin system and the many independent tissue renin-angiotensin systems is their interactions at multiple levels with reproduction. These interactions, which have received relatively little attention, include effects of estrogens and possibly androgens on hepatic and renal angiotensinogen mRNA; effects of androgens on the Ren-2 gene and salivary renin in mice; the prorenin surge that occurs with but outlasts the LH surge during the menstrual cycle; the inhibitory effects of estrogens on thirst and water intake; the tissue renin-angiotensin systems in the brain, the anterior pituitary, and the ovaries and testes, that is, in all the components of the hypothalamo-pituitary-gonadal axis; the presence of some components of the renin-angiotensin system in the uterus and the fetoplacental unit; and the possible relation of renin and angiotensin to ovulation and fetal well-being. These interactions are described and their significance considered in this short review.

  9. Reproduction and the renin-angiotensin system

    Science.gov (United States)

    Ganong, W. F.

    1995-01-01

    A unique aspect of the circulating renin-angiotensin system and the many independent tissue renin-angiotensin systems is their interactions at multiple levels with reproduction. These interactions, which have received relatively little attention, include effects of estrogens and possibly androgens on hepatic and renal angiotensinogen mRNA; effects of androgens on the Ren-2 gene and salivary renin in mice; the prorenin surge that occurs with but outlasts the LH surge during the menstrual cycle; the inhibitory effects of estrogens on thirst and water intake; the tissue renin-angiotensin systems in the brain, the anterior pituitary, and the ovaries and testes, that is, in all the components of the hypothalamo-pituitary-gonadal axis; the presence of some components of the renin-angiotensin system in the uterus and the fetoplacental unit; and the possible relation of renin and angiotensin to ovulation and fetal well-being. These interactions are described and their significance considered in this short review.

  10. Reproduction and the renin-angiotensin system

    Science.gov (United States)

    Ganong, W. F.

    1995-01-01

    A unique aspect of the circulating renin-angiotensin system and the many independent tissue renin-angiotensin systems is their interactions at multiple levels with reproduction. These interactions, which have received relatively little attention, include effects of estrogens and possibly androgens on hepatic and renal angiotensinogen mRNA; effects of androgens on the Ren-2 gene and salivary renin in mice; the prorenin surge that occurs with but outlasts the LH surge during the menstrual cycle; the inhibitory effects of estrogens on thirst and water intake; the tissue renin-angiotensin systems in the brain, the anterior pituitary, and the ovaries and testes, that is, in all the components of the hypothalamo-pituitary-gonadal axis; the presence of some components of the renin-angiotensin system in the uterus and the fetoplacental unit; and the possible relation of renin and angiotensin to ovulation and fetal well-being. These interactions are described and their significance considered in this short review.

  11. The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

    Directory of Open Access Journals (Sweden)

    Künzel Heike

    2003-10-01

    Full Text Available Abstract Background Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS as 1. adrenocorticotropic hormone (ACTH is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR agonists 3. angiotensin II (ATII releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM-nonREM cycle. Methods Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD 53.3 ± 14.4 yr. and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.. After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h were used for statistical analysis, with analysis of co variance being performed with age as a covariate. Results No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p Conclusion Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression.

  12. (pro)renin receptor: A stable molecule

    OpenAIRE

    Wiwanitkit, Viroj

    2011-01-01

    Background: Basically, (pro)renin acts via a specific receptor, (pro)renin receptor (PRR) binding between renin and prorenin, its inactive proenzyme form. The study on the molecular level of PRR can give useful knowledge to help understand many renal disorders. Method: Here, the author focuses on the stability of the PRR molecule. The mutation prone positions within the PRR molecule was assessed using standard reference technique. Result: The study showed there is no identified mutation prone...

  13. The Effect of Moderate Hypothermia on Renin-Angiotensin – Aldosterone System in Male Rats

    Directory of Open Access Journals (Sweden)

    M. Kourosh Arami

    2004-04-01

    Full Text Available Hypothermia in nature occurs in hibernating animals. It has applications in medicine in open heart surgery,organ and connective tissue preserving, altitude medicine and geriatrics. Despite the vastness of studies on hypothermia many of its biologic and physiologic effects including endocrine system alterations are still poorly recognized. In this study the effect of hypothermia on renin- angiotensin-aldosterone axis was explored. Ten male wistar albino rats (mean age 5 months were anesthetized by intraperitoneal injection of chloralhydrat (0.5 m1/100gr body weight. Then animals were placed in hypothermia apparatus . Their body temperature were reduced to 250 C. AngiotensinI(ANGI and aldosterone (ALD levels of serum were measured by radioimmunoassay before and after hypothermia induction and once every 24 hours for three days. Plasma renin activity (PRA was also measured by using the standard formula of angiotensin determinates at two temperatures of 40C and 370C . The results showed that PRA,ANGI and ALD increased significantly immedietly after hypothermia (p<0.03. Later changes were followed as these factors decreased to basal level, except in the case of aldosterone which maintained its increased level significantly for 24 hours (p<0.05. It seems that moderate hypothermia have stimulatory effect on PRA,ANGI and ALD that results of this study confirm it.

  14. Plasma nitriding and plasma nitrocarburizing of electroplated hard chromium to increase the wear and the corrosion properties

    Energy Technology Data Exchange (ETDEWEB)

    Menthe, E.; Rie, K.-T. (Technische Univ. Braunschweig (Germany). Inst. fuer Oberflaechentechnik und Plasmatechnische Werkstoffentwicklung)

    1999-02-01

    We have investigated the effect of plasma nitriding and plasma nitrocarburizing on the microstructure and properties of electroplated chromium. Plasma nitriding and plasma nitrocarburizing are applied to 15-100 [mu]m thick electroplated hard chromium coatings to increase both the wear and the corrosion resistance. The properties of the plasma-modified hard chromium layers are characterized by measuring the wear resistance with a Taber wear tester and the corrosion resistance with a salt spray fog test. Cyclic voltammetry is performed in a standard electrochemical cell using a 0.5 M H[sub 2]SO[sub 4] solution acidified to pH 0.3. The compound layer after plasma nitriding consists of CrN and Cr[sub 2]N with a maximum hardness of about 1100 HK[sub 0.01]. After plasma nitrocarburizing, Cr[sub 3]C[sub 2] and Cr[sub 7]C[sub 3] are formed. After plasma nitrocarburizing, the maximum hardness is increased up to 2200 HK[sub 0.01]. The wear rate is reduced as compared to an untreated chromium layer. The exposure time in the salt spray fog, before corrosion products are visible can be increased by a factor of 5. The improvement in wear and corrosion resistance after plasma nitriding and plasma nitrocarburizing is discussed considering microstructural changes of the treated layer. (orig.) 10 refs.

  15. Prostaglandins, catecholamines, renin and aldosterone during hypertensive and normotensive pregnancy.

    Science.gov (United States)

    Pedersen, E B; Christensen, N J; Christensen, P; Johannesen, P; Kornerup, H J; Kristensen, S; Lauritsen, J G; Leyssac, P P; Rasmussen, A B; Wohlert, M

    1982-01-01

    Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

  16. Renin and prorenin receptor in hypertension: what's new?

    Science.gov (United States)

    Nguyen, Genevieve

    2011-02-01

    The (pro)renin receptor, PRR, was initially characterized as a component of the renin-angiotensin system (RAS). PRR-bound renin and prorenin display increased enzymatic activity, and binding activates intracellular signaling, upregulating the expression of profibrotic proteins. As a consequence, most studies set out to demonstrate a role of PRR in hypertension, cardiovascular and renal diseases, and organ damage, and to identify PRR as a therapeutic target to optimize RAS blockade. The results of animal studies were disappointing and did not convincingly establish PRR as major player in hypertension or in organ damage, although human studies suggested a link between a polymorphism in the PRR gene and blood pressure. New data now suggest that PRR is functionally linked to the vacuolar proton-ATPase and, quite unexpectedly, that PRR is necessary to Wnt signaling pathways that are essential (independently of renin) for adult and embryonic stem cell biology, embryonic development, and diseases including cancer, thereby opening new perspectives on the pathophysiological roles of PRR.

  17. Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist.

    Science.gov (United States)

    Sato, Atsuhisa; Fukuda, Seiichi

    2013-10-01

    We have reported observing aldosterone breakthrough in the course of relatively long-term treatment with renin-angiotensin (RA) system inhibitors, where the plasma aldosterone concentration (PAC) increased following an initial decrease. Aldosterone breakthrough has the potential to eliminate the organ-protective effects of RA system inhibitors. We therefore conducted a study in essential hypertensive patients to determine whether aldosterone breakthrough occurred during treatment with the direct renin inhibitor (DRI) aliskiren and to ascertain its clinical significance. The study included 40 essential hypertensive patients (18 men and 22 women) who had been treated for 12 months with aliskiren. Aliskiren significantly decreased blood pressure and plasma renin activity (PRA). The PAC was also decreased significantly at 3 and 6 months; however, the significant difference disappeared after 12 months. Aldosterone breakthrough was observed in 22 of the subjects (55%). Urinary albumin excretion differed depending on whether breakthrough occurred. For the subjects in whom aldosterone breakthrough was observed, eplerenone was added. A significant decrease in urinary albumin excretion was observed after 1 month, independent of changes in blood pressure. In conclusion, this study demonstrated that aldosterone breakthrough occurs in some patients undergoing DRI therapy. Aldosterone breakthrough affects the drug's ability to improve urinary albumin excretion, and combining a mineralocorticoid receptor antagonist with the DRI may be useful for decreasing urinary albumin excretion. When the objective is organ protection in hypertensive patients, a two-pronged approach using combination therapy to inhibit both the RA system and aldosterone may be highly effective.

  18. Serum sodium levels of heart failure and its influence on plasma renin-angiotensin-aldosterone system and brain natriuretic peptide levels%心力衰竭血钠水平对 RAAS 及 BNP 水平的影响

    Institute of Scientific and Technical Information of China (English)

    王玉东; 任松涛; 蔡青云

    2014-01-01

    Objective To study the correlation between serum sodium levels of heart failure and plasma renin-angiotensin-aldosterone system( PAAS) and brain natriuretic peptide(BNP) levels . Methods 122 122 patients with heart failure were divided into control ( serum sodium concentration<135 mmol/L ,57 cases) and observation group ( serum sodium concentration≥135 mmol/L , 65 cases) according to serum sodium levels . PRA , Ang Ⅱ , ALD and BNP levels of two groups were compared and analyzed , the correlation between serum sodium levels and levels of PRA ,AngⅡ ,ALD and BNP were analyzed by Pearson correlation analysis . Results Levels of PRA , Ang Ⅱ ,ALD and BNP of observation group were higher than that in control group significantly( P < 0 .05 ) .Pearson correlation analysis showed , serum sodium levels was positively correlated with levels of PRA , Ang Ⅱ , ALD and BNP( P <0 .05 ) .Conclusion Low level serum sodium of heart failure promotes the release of PRA , Ang , ALD and BNP , serum sodium levels is positively correlated with levels of PRA , Ang Ⅱ , ALD and BNP .%目的:研究心力衰竭患者血钠水平与血浆肾素-血管紧张素-醛固酮系统(RAAS)及脑钠肽之间(BNP)的相关性。方法选择我院收治的122例心力衰竭患者,根据血钠水平分为对照组(血清钠离子浓度<135 mmol/L ,57例)和观察组(血清钠离子浓度≥135 mmol/L ,65例),对2组患者的肾素(PRA)、血管紧张素(AngⅡ)、醛固酮(ALD)及BNP水平进行比较分析,并对血钠水平与AngⅡ、ALD及BNP水平的相关性采用 Pearson相关分析。结果观察组的PRA、AngⅡ、ALD及BNP水平显著高于对照组,差异具有统计学意义(P <00.5),通过 Pearson相关分析可见,患者的血钠水平与PRA、AngⅡ、ALD及BNP水平均呈负相关( P <00.5)。结论心力衰竭患者血钠水平低时能促进PRA、AngⅡ、ALD及BNP的释放,且血钠水平

  19. Hyperpotassemia and bradycardia in a bedridden elderly woman with selective hypoaldosteronism associated with low renin activity.

    Science.gov (United States)

    Inada, Mitsuo; Iwasaki, Keiko; Imai, Chihiro; Hashimoto, Satoshi

    2010-01-01

    A bedridden 85-year-old woman had hyperpotassemia (7.7 mEq/L) and bradycardia (30/min). Endocrinologic findings revealed a decrease in the renin-aldosterone system and normal adrenoglucocorticoid function. The results were consistent with the abnormalities seen in selective hypoaldosteronism with low renin activity. In addition, 9 of 11 patients, selected randomly from 72 bedridden elderly patients with normal serum sodium and potassium levels in our hospital, had diminished plasma renin activity (PRA) and plasma aldosterone concentration (PAC). The present patient was prescribed nonsteroidal anti-inflammatory drug (NSAID). NSAID reduces renal potassium excretion through the inhibition of renal prostaglandin synthesis. Therefore, the use of NSAID in bedridden elderly patients might intensify the underlying asymptomatic hypoaldosteronism and cause life-threatening hyperpotassemia.

  20. Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

    Directory of Open Access Journals (Sweden)

    Claus Brandt

    2014-01-01

    Full Text Available Background. Rodent models suggest that follistatin-like 3 (fstl3 is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation. Objective. To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. Study Design. Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS, TNF-α, or interleukin-6 (IL-6 as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans. Results. Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans. Conclusion. Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3.

  1. Responsiveness of the renin-aldosterone system during exercise in young patients with essential hypertension.

    Science.gov (United States)

    Pedersen, E B; Kornerup, H J; Larsen, J S

    1981-10-01

    The effect of exercise of gradually increased intensity, i.e. 75 W for 20 min followed by 100 W for 20 min, on plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) was studied in young patients with essential hypertension and normotensive control subjects. During exercise without previous sodium loading PRC and PAC increased to the same degree in both hypertensives and normotensives during light exercise; PRC increased further significantly in the normotensives (63 to 72 microIU/ml (medians), P less than 0.01) but not in the hypertensives (46 to 51 microIU/ml) during heavy exercise. PRC and PAC were significantly correlated during both 75 W (rho = 0.633, P less than 0.05) and 100 W (rho = 0.635, P less than 0.05) exercise in the normotensives, but not in the hypertensives. During exercise after loading with 500 ml sodium chloride (0.85 mol/l) PRC and PAC increased in both hypertensives (28 to 42 microIU/ml, P less than 0.01; 0.11 to 0.53 nmol/l, P less than 0.01) and normotensives (22 to 33 microIU/ml, P less than 0.02; 0.12 to 0.34 nmol/l, P less than 0.01), although to a considerably lower degree than without previous loading. PRC and PAC were, however, significantly higher in the hypertensive than in the normotensive group after exercise. It is suggested that the responsiveness of the renin-aldosterone system is abnormal during exercise in young patients with mild essential hypertension, both without and with previous intravenous sodium loading.

  2. Hereditary increase of plasma histidine-rich glycoprotein associated with abnormal heparin binding (HRG Eindhoven).

    Science.gov (United States)

    Hoffmann, J J; Hennis, B C; Kluft, C; Vijgen, M

    1993-12-20

    Plasma histidine-rich glycoprotein (HRG) was found to be persistently increased in a patient with a history of recurrent arterial thromboembolic events. The mean concentration was 270% of normal pooled plasma. Increased HRG was found in eight of the 17 relatives studied, but none of them has experienced thrombo-embolism yet. Apparently, increased HRG was hereditary with autosomal dominant inheritance. A significant correlation was found between the increased plasma concentration of the protein and the age of the subjects (P Eindhoven.

  3. Prorenin receptor regulates more than the renin-angiotensin system.

    Science.gov (United States)

    Müller, Dominik N; Binger, Katrina J; Riediger, Fabian

    2012-06-01

    The (pro)renin receptor (PRR) was initially believed to be a contributor to the pathogenesis of cardiovascular diseases via the amplification of renin- or prorenin-induced angiotensin (Ang) formation. However, a recent paradigm shift suggests a new role for PRR, separate from the renin-angiotensin system (RAS), in contributing to cellular homeostasis. Specifically, PRR is thought to be essential for vacuolar H(+) -ATPase (V-ATPase) activity and acts as an adaptor between the V-ATPase and the Wnt signalling pathway. Recent PRR conditional knock-out studies have confirmed this link between V-ATPase and PRR, with deletion resulting in the accumulation of autophagic vacuoles and animal lethality. The molecular mechanism by which PRR contributes to V-ATPase activity, and whether multiple signalling pathways are affected by PRR loss, is currently unknown. Additionally, cleavage by furin at a single site within full-length PRR results in the production of a soluble form of the receptor, which is detectable in plasma. Soluble PRR is hypothesized to bind to specific ligands and receptors and mediate signal transduction pathways. Understanding the physiological function of full-length and soluble PRR will be important for establishing its role in pathology.

  4. Lead, hypertension, and the renin-angiotensin system in rats

    Energy Technology Data Exchange (ETDEWEB)

    Victery, W.; Vander, A.J.; Shulak, J.M.; Schoeps, P.; Julius, S.

    1982-03-01

    Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 100, or 500 ppm Pb (as Pb acetate) and then continuing this regimen after weaning. Male rats receiving 100 ppm developed a significant elevation of systolic blood pressure (152 +/- 3.7 mm Hg vs. 135 +/- 5.6 for controls) at 3 1/2 months and remained hypertensive until sacrifice at 6 months; 500 ppm rats remained normotensive. Both 100 ppm and 500 ppm females remained normotensive. At 6 months plasma renin activity (PRA) was significantly reduced in the 100 ppm male group but was normal in the 500 ppm group. There was dose-dependent decreases in the All/PRA ratio and in renal renin. Pulmonary converting enzyme activity was not changed by Pb exposure. Blood (Pb) was 40 and 71 ..mu..g/dl, respectively, and kidney (Pb) was 4.8 and 22.9 ..mu..g/gm. Renal histology was normal in the 100 ppm group. We conclude that doses of Pb which produce blood (Pb) seen in many people are capable of including modest hypertension in male rats; higher doses fail to do so. The hypertension is associated with a reduction in PRA and All and therefore is unlikely to be due to hyperactivity of the renin-angiotensin system (RAS).

  5. Stimulatory effects of neuronally released norepinephrine on renin release in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Yasuo; Kawazoe, Shinka; Ichihara, Toshio; Shinyama, Hiroshi; Kageyama, Masaaki; Morimoto, Shiro (Osaka Univ. of Pharmaceutical Sciences (Japan))

    1988-10-01

    Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. The authors found that the decreased response of renin release from rat kidney cortical slices in high potassium solution changed to a strikingly increased one in the presence of nifedipine at doses over 10{sup {minus}6} M. They then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd{sup 2+}, Co{sup 2+}, and Mn{sup 2+} blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in {sup 3}H efflux from the slices preloaded with ({sup 3}H)-norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of {beta}-adrenoceptors.

  6. Renin system of the kidney in ISIAH rats with inherited stress-induced arterial hypertension.

    Science.gov (United States)

    Fedoseeva, L A; Dymshits, G M; Markel, A L; Jakobson, G S

    2009-02-01

    The renal renin system was studied in ISIAH rats with inherited stress-induced arterial hypertension. The expression of genes for renin (Ren1) and cyclooxygenase (Cox-2) was evaluated in renal tissue of ISIAH and WAG rats (normotensive control). Basal gene expression for Ren1 and Cox-2 in ISIAH rats was much lower than in WAG rats. Water deprivation for 11 h was followed by a 4-fold increase in Cox-2 gene expression in ISIAH rats. The increase in gene expression was insignificant in WAG rats (by 30%). Renin gene expression in renal tissue of ISIAH and WAG rats remained practically unchanged after water deprivation. We conclude that a change in Cox-2 gene expression after short-term water deprivation serves as a reliable criterion for functional strain of the renal renin system in hypertensive ISIAH rats.

  7. Relation of central alpha-adrenoceptor and other receptors to the control of renin secretion.

    Science.gov (United States)

    Ganong, W F

    1983-02-01

    The location and nature of the receptors in the brain on which clonidine acts to decrease renin secretion have been investigated in dogs. Clonidine was injected into the vertebral and carotid arteries, and its effects were compared with those of norepinephrine and epinephrine when injected into the third ventricle. It was also injected intravenously (IV) after transection of the brain stem and following treatment with intraventricular 6-hydroxydopamine. The results suggest that the renin-regulating receptors are located in the brain stem in a region different from the receptors mediating the depressor response, that they are alpha 2-adrenoceptors, and that they are postsynaptic in location. Central alpha 1-adrenoceptors appear to mediate increased renin secretion. Central serotonergic receptors also mediate increased renin secretion, but it is not known how the alpha 1- and alpha 2-adrenoceptors interact with the serotonergic systems.

  8. Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations▿

    OpenAIRE

    Hynninen, V. V.; Olkkola, K T; Bertilsson, L; Kurkinen, K. J.; Korhonen, T; Neuvonen, P. J.; Laine, K

    2008-01-01

    This study investigated the effect of voriconazole, an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4, and itraconazole, an inhibitor of CYP3A4, on the pharmacokinetics and pharmacodynamics of meloxicam. Twelve healthy volunteers in a crossover study ingested 15 mg of meloxicam without pretreatment (control), after voriconazole pretreatment, and after itraconazole pretreatment. The plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B2 (TxB2) generation were ...

  9. A Case of Ectopic Renin-secreting Orbital Hemangiopericy-toma Associated with Juvenile Hypertension and Hypokalemia

    Directory of Open Access Journals (Sweden)

    Yokoyama,Hisamitsu

    1979-08-01

    Full Text Available An unusual case of orbital tumor with high renin content and severe hypertension is described. The patient was a 15-year-old girl with juvenile hypertension (200-140 mmHg associated with right exophthalmos and hypokalemia. The patient showed extremely high levels of plasma renin activity and plasma aldosterone concentration. No difference was present in plasma renin activity from either side of the renal veins. Preoperatively, hypertension responded to treatment with spironolactone. The tumor could not be completely removed because of intracranial metastasis and infiltration, and the hyperreninemia and secondary hyperaldosteronism persisted. The renin content in the orbital tissue was 1,403-2,225 ng/angiotensin I generated/h/g wet weight of tissue. The postmortem histopathologic diagnosis was orbital hemangiopericytoma. This is the first case of extrarenal (ectopic renin-secreting (or -producing hemangiopericytoma of the orbital origin. Furthermore this case is worthy of note in the point of view of the presence of the extrarenal renin-angiotensin system, particularly in the brain.

  10. [24-hour systolic wave increment index monitoring in patients with low-renin arterial hypertension].

    Science.gov (United States)

    Valieva, Z S; Chikhladze, N M; Rogoza, A N; Iarovaia, E B; Bosykh, E G; Chazova, I E

    2014-01-01

    To analyze the circadian rhythm of blood pressure (BP) and daily reflected wave values in patients with low-renin hypertension with normal and elevated aldosterone production. The investigation included 66 patients. 24-hour BP monitoring was carried out and arterial wall rigidity and reflected wave values were assessed in all the patients. The patients with hyperaldosteronemia were found to have not only statistically significant severer hypertension, impaired circadian rhythms of BP, but also impaired augmentation index (Aix)--mainly its nocturnal increase. A positive correlation was found between nocturnal Aix and resting plasma aldosterone concentrations (r = -0.31; p = 0.002). The findings suggest the expediency of 24-hour systolic wave increment index monitoring in hypertensive patients ofthis category.

  11. (Pro)renin and its receptors: Pathophysiological implications

    NARCIS (Netherlands)

    W.W. Batenburg (Wendy); A.H.J. Danser (Jan)

    2012-01-01

    textabstractTissue angiotensin generation depends on the uptake of circulating (kidney-derived) renin and/or its precursor prorenin [together denoted as (pro)renin]. Since tissue renin levels are usually somewhat higher than expected based upon the amount of (renin-containing) blood in tissue, an

  12. Leptin Mediates High-Fat Diet Sensitization of Angiotensin II-Elicited Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation.

    Science.gov (United States)

    Xue, Baojian; Yu, Yang; Zhang, Zhongming; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Felder, Robert B; Johnson, Alan Kim

    2016-05-01

    Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high-fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin II administration that is mediated at least, in part, by increased activity of brain renin-angiotensin system and proinflammatory cytokines. This study tested whether leptin mediates this HFD-induced sensitization of angiotensin II-elicited hypertension by interacting with brain renin-angiotensin system and proinflammatory cytokine mechanisms. Rats fed an HFD for 3 weeks had significant increases in white adipose tissue mass, plasma leptin levels, and mRNA expression of leptin and its receptors in the lamina terminalis and hypothalamic paraventricular nucleus. Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD sensitization of angiotensin II-elicited hypertension. Furthermore, central infusion of leptin mimicked the sensitizing action of HFD. Concomitant central infusions of the angiotensin II type 1 receptor antagonist irbesartan, the tumor necrosis factor-α synthesis inhibitor pentoxifylline, or the inhibitor of microglial activation minocycline prevented the sensitization produced by central infusion of leptin. RT-PCR analysis indicated that either HFD or leptin administration upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus. The leptin antagonist and the inhibitors of angiotensin II type 1 receptor, tumor necrosis factor-α synthesis, and microglial activation all reversed the expression of these genes. The results suggest that HFD-induced sensitization of angiotensin II-elicited hypertension is mediated by leptin through upregulation of central renin-angiotensin system and proinflammatory cytokines.

  13. Ethanol increases plasma vasopressin shortly after intraperitoneal injection in rats

    Energy Technology Data Exchange (ETDEWEB)

    Colbern, D.L.; ten Haaf, J.; Tabakoff, B.; van Wimersma Greidanus, T.B.

    1985-09-16

    In rats, ethanol has generally been thought to inhibit vasopressin (VP) release into the peripheral circulation; however, the primary evidence for this conclusion has been indirect. Radioimmunoassay was used to measure VP in the plasma of rats decapitated 5 or 60 min after intraperitoneal injection of ethanol (2.0 g/kg). Confirming the popular notion that ethanol inhibits VP release, VP levels were decreased 60 min after treatment. But radioimmunoassay techniques also revealed that VP release is markedly stimulated shortly after an injection of ethanol. 14 references, 1 figure.

  14. Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Walkiria Wingester Vilas-Boas; Ant(o)nio Ribeiro-Oliveira Jr; Renata da Cunha Ribeiro; Renata Lúcia Pereira Vieira; Jerusa Almeida; Ana Paula Nadu; Ana Cristina Sim(o)es e Silva; Robson Augusto Souza Santos

    2008-01-01

    AIM: To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS: Patients were allocated into two groups: outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA), Angiotensin(Ang) Ⅰ, Ang Ⅱ, and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation, hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components.RESULTS: PRA, Ang Ⅰ, Ang Ⅱ and Ang-(1-7) were significantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang Ⅰ levels and between Ang Ⅱ and Ang Ⅰ were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang Ⅱ remained unchanged in splanchnic and peripheral circulation in patients under 13-blockade, whereas the relationship between Ang Ⅱ and Ang Ⅰ was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation, cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup.CONCLUSION: In LD group, propranolol treatment reduced RAS mediators, but did not change the ratio between Ang-(1-7) and Ang Ⅱ in splanchnic and peripheral circulation. Furthermore, the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio.

  15. Aliskiren accumulation in the kidney : no major role for binding to renin or prorenin

    NARCIS (Netherlands)

    Lange, Sascha; Fraune, Christoph; Alenina, Natalia; Bader, Michael; Danser, A. H. Jan; Frenay, Anne-Roos; van Goor, Harry; Stahl, Rolf; Nguyen, Genevieve; Schwedhelm, Edzard; Wenzel, Ulrich Otto

    2013-01-01

    Background and objective: The antihypertensive effects of the direct renin inhibitor aliskiren last substantially longer after treatment withdrawal than expected based upon its plasma half-life. This may be attributable to drug accumulation in the kidney as recently shown in rats and mice. Since ali

  16. FABP4 plasma levels are increased in familial combined hyperlipidemia

    Science.gov (United States)

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L.; Ascaso, Juan F.; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-01-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia. PMID:20388924

  17. Glycoprotein fucosylation is increased in seminal plasma of subfertile men

    Directory of Open Access Journals (Sweden)

    Beata Olejnik

    2015-04-01

    Full Text Available Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL. Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade.

  18. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

    Science.gov (United States)

    Ma, Jinhui; Guo, Wanshou; Li, Zirong; Li, Shirui; Wang, Peng

    2017-01-01

    The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH). Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI-) matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH. PMID:28167850

  19. Mechanisms of renin release from juxtaglomerular cells

    DEFF Research Database (Denmark)

    Skøtt, O; Salomonsson, Max; Sellerup Persson, Anja;

    1991-01-01

    In microdissected, nonperfused afferent arterioles changes in intravascular pressure did not affect renin secretion. On the contrary, renin release from isolated afferent arterioles perfused in a free-flow system has been reported to be sensitive to simultaneous changes in luminal pressure and flow....... Hence local blood flow may be involved in the baroreceptor control of renin release. If flow is sensed, the sensor is likely to be located near the endothelial cell layer, where ion channels have been shown to be influenced by variations in shear stress....

  20. Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage.

    Science.gov (United States)

    Schoenhals, Matthieu; Jourdan, Michel; Seckinger, Anja; Pantesco, Véronique; Hose, Dirk; Kassambara, Alboukadel; Moreaux, Jérôme; Klein, Bernard

    2016-07-17

    A role of the transcription factor Krüppel-like factor 4 (KLF4) in the generation of mature plasma cells (PC) is unknown. Indeed, KLF4 is critical in controlling the differentiation of various cell linages, particularly monocytes and epithelial cells. KLF4 is expressed at low levels in pro-B cells and its expression increases as they mature into pre-B cells, resting naïve B cells and memory B cells. We show here that KLF4 is expressed in human bone marrow plasma cells and its function was studied using an in vitro model of differentiation of memory B cells into long lived plasma cells. KLF4 is rapidly lost when memory B cells differentiate into highly cell cycling plasmablasts, poorly cycling early plasma cells and then quiescent long-lived plasma cells. A forced expression of KLF4 in plasmablasts enhances the yield of their differentiation into early plasma cell and long lived plasma cells, by inhibiting apoptosis and upregulating previously unknown plasma cell pathways.

  1. Clinical pharmacology of single- and multiple-ascending doses of ACT-178882, a new direct renin inhibitor, and its pharmacokinetic interaction with food and midazolam.

    Science.gov (United States)

    Dingemanse, Jasper; Nicolas, Laurent; Binkert, Christoph

    2013-12-01

    This study investigated the tolerability, safety, pharmacokinetics, and pharmacodynamics of ACT-178882, a new direct renin inhibitor, as well as its interaction with food and midazolam. Healthy male subjects received either single (10-1000 mg) or multiple doses (30-600 mg) administered once daily for 14 days of ACT-178882, placebo, or 20 mg enalapril in the fasted state. Following a 2-week washout, the single dose of 30 mg ACT-178882 was also administered in the fed state. In the multiple-ascending-dose part, subjects were dosed with midazolam on days -2, 2, and 12 to investigate interactions with CYP3A4. Dizziness and headache were the most frequently reported adverse events. No clinically relevant changes occurred for body weight, vital signs, clinical laboratory variables, and ECG although both enalapril and ACT-178882 tended to decrease systolic blood pressure. Following single doses of ACT-178882, t1/2 and tmax varied from 18.7 to 24.7 h and from 3 to 5 h, respectively, and food had no significant effect. Steady-state conditions were achieved after 4-6 days of dosing and accumulation was minimal. ACT-178882 pharmacokinetics were dose proportional. ACT-178882 but not enalapril dose-dependently increased Cmax and area under the concentration-time curve of midazolam. Single and multiple doses of ACT-178882 dose-dependently increased active renin and decreased plasma renin activity, whereas enalapril increased both variables. No effects on urinary excretion of creatinine, potassium, and the 6β-hydroxycortisol/cortisol ratio were observed, whereas sodium and aldosterone excretion was decreased by both ACT-178882 and enalapril. The current results with ACT-178882 warrant further clinical investigation of this renin inhibitor in hypertensive patients.

  2. Does Extremely Low Birth Weight Predispose to Low-Renin Hypertension?

    Science.gov (United States)

    Raaijmakers, Anke; Zhang, Zhen-Yu; Claessens, Jolien; Cauwenberghs, Nicholas; van Tienoven, Theun Pieter; Wei, Fang-Fei; Jacobs, Lotte; Levtchenko, Elena; Pauwels, Steven; Kuznetsova, Tatiana; Allegaert, Karel; Staessen, Jan A

    2017-03-01

    Low birth weight and prematurity are risk factors for hypertension in adulthood. Few studies in preterm or full-term born children reported on plasma renin activity (PRA). We tested the hypothesis that renin might modulate the incidence of hypertension associated with prematurity. We enrolled 93 prematurely born children with birth weight hypertension associated with extreme low birth weight were 6.43 (2.52-16.4; Phypertension, but does not affect the inverse association between PRA and BP. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147457. © 2017 American Heart Association, Inc.

  3. Neural Mechanism by which Gravitational Stimuli and Stress Affect the Secretion of Renin and Other Hormones

    Science.gov (United States)

    Ganong, W. F.; Gotoh, E.; Alper, R. H.

    1985-01-01

    The serotonin-releasing drug p-chloroamphetamine (PCA), as well as L-propranolol and chloriasondamine were used in a study which established that the pathway from the hypothalamus to the kidneys is sympathetic. Which hypothalamic nuclei mediate the response to PCA is being investigated experiments are being conducted to determine a readily reproducible psychological stimulus to renin secretion that can be used in rats. The effects of equithesin, urethane, and inactin on plasma renin activity were examined in preparation for tilting experiments. The relation of vasopressin-secreting neurons in the brain sem to PCA response was explored in Brattleboro rats that are congenitally unable to produce vasopressin in their hypothalami.

  4. Neural Mechanism by which Gravitational Stimuli and Stress Affect the Secretion of Renin and Other Hormones

    Science.gov (United States)

    Ganong, W. F.; Gotoh, E.; Alper, R. H.

    1985-01-01

    The serotonin-releasing drug p-chloroamphetamine (PCA), as well as L-propranolol and chloriasondamine were used in a study which established that the pathway from the hypothalamus to the kidneys is sympathetic. Which hypothalamic nuclei mediate the response to PCA is being investigated experiments are being conducted to determine a readily reproducible psychological stimulus to renin secretion that can be used in rats. The effects of equithesin, urethane, and inactin on plasma renin activity were examined in preparation for tilting experiments. The relation of vasopressin-secreting neurons in the brain sem to PCA response was explored in Brattleboro rats that are congenitally unable to produce vasopressin in their hypothalami.

  5. A Study on Renin-Angiotensin System and Total Exchangeable Sodium in Hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Kang Won; Park, Jung Sik; Lee, Jung Sang; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1976-03-15

    The etiologic role of renin-angiotensin system and sodium-volume status in the pathophysiology of various forms of hypertension was investigated. Plasma renin activity (PRA) was measured by radioimmunoassay, while sodium-volume status was evaluated by the determination of total exchangeable sodium(NaE) using isotope dilution method. The subjects consisted of 25 controls, 24 patients with essential hypertension, 22 patients with chronic renal failure (13 with hypertension, 9 without hypertension) and 14 patients with malignant hypertension. The results were as follows: 1) An inverse correlation between NaE and PRA was noted in control subjects (r=-0.598, p<0.001) and normal renin essential hypertension(r=-0.551, p<0.05) and the chronic renal failure with hypertension. (r=-0.790, P<0.001) 2) NaE increased markedly the in chronic renal failure with hypertension (66.9+-8.69 mEq/kg of LBM, p<0.001) and the chronic renal failure without hypertension (54.9+-9.28 mEq/kg of LBM, p<0.05), while mild increase was noted in malignant hypertension (51.7+-6.24 mEq/kg of LBM, 0.05renin subgroups.(p>0.1) 3) Absolute value of PRA was not deviated significantly from control group (2.53+-1.416 ng/ml/hr) except in malignant hypertension (6.09+-2.042, p<0.001). But PRA was inappropriately high in relation to prevailing NaE in the chronic renal failure with hypertension (eleven of thirteen patients) and malignant hypertension (ten of fourteen patients), while PRA variatiation was within physiologic range in the chronic renal failure without hypertension. 4) The NaE-PRA product was markedly increased in the chronic renal failure with hypertension (514.4+-42.10, p<0.001) and in malignant hypertension (442.7+-55.03, p<0.001), while moderately increased NaE-PRA product was noted in the chronic renal failure without hypertension (402.6+-59.67, p<0

  6. Influência do exercício aeróbio na renina de portadores de hipertensão arterial com sobrepeso Influencia del ejercicio aeróbico en la renina de portadores de hipertensión arterial con sobrepeso Effect of aerobic exercise on plasma renin in overweight patients with hypertension

    Directory of Open Access Journals (Sweden)

    Bruno Martinelli

    2010-07-01

    Full Text Available FUNDAMENTO: A atividade do sistema renina-angiotensina-aldosterona tem relação direta com sobrepeso e sedentarismo, e essas variáveis se associam à hipertensão arterial (HA. O exercício aeróbio propicia melhor controle da pressão arterial (PA por agir nos mecanismos da regulação pressórica, dentre eles, a atividade de renina plasmática (ARP. OBJETIVO: Avaliar a influência do exercício aeróbio sobre ARP em portadores de HA com sobrepeso. MÉTODOS: Foram avaliados níveis pressóricos, bioquímicos e antropométricos pré e pós-treinamento de 16 semanas, três vezes por semana, a 60%-80% da frequência cardíaca máxima. Os dados foram expressos em média ± desvio padrão ou mediana e intervalo interquartílico, e analisados pelo teste "t", Mann-Withney e ANOVA (p FUNDAMENTO: La actividad del sistema renina-angiotensina-aldosterona tiene relación directa con sobrepeso y sedentarismo, y esas variables se asocian a la hipertensión arterial (HA. El ejercicio aeróbico propicia mejor control de la presión arterial (PA por actuar en los mecanismos de la regulación presórica, entre ellos, la actividad de renina plasmática (ARP. OBJETIVO: Evaluar la influencia del ejercicio aeróbico sobre ARP en portadores de HA con sobrepeso. MÉTODOS: Fueron evaluados niveles presóricos, bioquímicos y antropométricos pre y post-entrenamiento de 16 semanas, tres veces por semana, a 60%-80% da frecuencia cardíaca máxima. Los datos fueron expresados en media ± desvío estándar o media e intervalo intercuartílico, y analizados por el teste "t", Mann-Withney y ANOVA (p BACKGROUND: The activity of the renin-angiotensin-aldosterone system (RAAS is directly related to overweight and sedentary lifestyles, both of which are associated with hypertension. Aerobic exercise helps control blood pressure (BP by acting on mechanisms of blood pressure regulation, such as plasma renin activity (PRA. OBJECTIVE: To assess the effect of aerobic exercise on

  7. Renin-angiotensin system gene polymorphisms and endometrial cancer.

    Science.gov (United States)

    Pringle, Kirsty G; Delforce, Sarah J; Wang, Yu; Ashton, Katie A; Proietto, Anthony; Otton, Geoffrey; Blackwell, C Caroline; Scott, Rodney J; Lumbers, Eugenie R

    2016-05-01

    Endometrial cancer (EC) is the most common gynaecological malignancy and its incidence is increasing. Dysregulation of the endometrial renin-angiotensin system (RAS) could predispose to EC; therefore, we studied the prevalence of RAS single nucleotide polymorphisms (SNPs) in Australian women with EC. SNPs assessed were AGT M235T (rs699); AGTR1 A1166C (rs5186); ACE A240T and T93C (rs4291, rs4292) and ATP6AP2 (rs2968915). They were identified using TaqMan SNP Genotyping Assays. The C allele of the AGTR1 SNP (rs5186) was more prevalent in women with EC (odds ratio (OR) 1.7, 95% confidence interval (CI) (1.2-2.3), P=0.002). The CC genotype of this SNP is associated with upregulation of the angiotensin II type 1 receptor (AGTR1). The G allele of AGT rs699, which is associated with higher angiotensinogen (AGT) levels, was less prevalent in women with EC (OR 0.54, 95% CI (0.39-0.74), P<0.001) compared with controls. AGT and AGT formed by removal of angiotensin I (des(Ang I)AGT) are both anti-angiogenic. In women with EC who had had hormone replacement therapy (HRT), the prevalence of the AGTR1 SNP (rs5186) and the ACE SNPs (rs4291 and rs4292) was greater than in women who had no record of HRT; SNP rs4291 is associated with increased plasma ACE activity. These data suggest there is an interaction between genotype, oestrogen replacement therapy and EC. In conclusion, the prevalence of two SNPs that enhance RAS activity was different in women with EC compared with healthy controls. These genetic factors may interact with obesity and hyperoestrogenism, predisposing ageing, obese women to EC.

  8. Pedophilia is accompanied by increased plasma concentrations of catecholamines, in particular epinephrine.

    Science.gov (United States)

    Maes, M; De Vos, N; Van Hunsel, F; Van West, D; Westenberg, H; Cosyns, P; Neels, H

    2001-08-05

    Plasma epinephrine and norepinephrine concentrations were measured in pedophiles and normal men both in placebo conditions and after administration of meta-chlorophenylpiperazine (mCPP), a post-synaptic 5-HT2 receptor agonist. The plasma concentrations of catecholamines, in particular epinephrine, were significantly increased in pedophiles. It is concluded that pedophiles may have an increased activity of the sympathoadrenal system.

  9. Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Dhamrait, Sukhbir S.; Sethi, Amar A

    2008-01-01

    BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system...... are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma...... angiotensinogen concentration and serum ACE activity. RESULTS: Three risk factors for severe hypoglycemia were identified: plasma angiotensinogen concentration in the upper quartile (relative rate [RR] vs. lower quartile 3.1, 95% confidence interval [CI,] 1.4-6.8), serum ACE activity in the upper quartile (RR vs...

  10. Association between the intrarenal renin-angiotensin system and renal injury in chronic kidney disease of dogs and cats.

    Science.gov (United States)

    Mitani, Sawane; Yabuki, Akira; Taniguchi, Kazuyuki; Yamato, Osamu

    2013-02-01

    The association of renin and angiotensin II, which are potent components of the renin-angiotensin system, with the severity of chronic renal disease was investigated immunohistochemically in dogs and cats. Immunoreactivities of renin and angiotensin II were evaluated quantitatively, and their correlations with the degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration and interstitial fibrosis were statistically analyzed. Immunoreactivities for renin were detected in afferent arteries in both dogs and cats. The score of renin-positive signals showed no correlation with plasma creatinine concentration or any of the histopathological parameters, except for the diameter of glomeruli in dogs. Immunoreactivities for angiotensin II were detected in tubules (primarily proximal tubules) and interstitial mononuclear cells in both dogs and cats. The score of tubular angiotensin II correlated with glomerulosclerosis and cell infiltration in cats but not in dogs. The score of interstitial angiotensin II correlated with plasma creatinine concentration, glomerulosclerosis, cell infiltration and fibrosis in dogs and with glomerulosclerosis and cell infiltration in cats. In conclusion, the results of the study suggest that intrarenal renin-angiotensin system is correlated with the severity of kidney disease, with the underlying mechanism differing between dogs and cats.

  11. Effects of direct Renin inhibition on myocardial fibrosis and cardiac fibroblast function.

    Directory of Open Access Journals (Sweden)

    Hui Zhi

    Full Text Available Myocardial fibrosis, a major pathophysiologic substrate of heart failure with preserved ejection fraction (HFPEF, is modulated by multiple pathways including the renin-angiotensin system. Direct renin inhibition is a promising anti-fibrotic therapy since it attenuates the pro-fibrotic effects of renin in addition to that of other effectors of the renin-angiotensin cascade. Here we show that the oral renin inhibitor aliskiren has direct effects on collagen metabolism in cardiac fibroblasts and prevented myocardial collagen deposition in a non-hypertrophic mouse model of myocardial fibrosis. Adult mice were fed hyperhomocysteinemia-inducing diet to induce myocardial fibrosis and treated concomitantly with either vehicle or aliskiren for 12 weeks. Blood pressure and plasma angiotensin II levels were normal in control and hyperhomocysteinemic mice and reduced to levels lower than observed in the control group in the groups treated with aliskiren. Homocysteine-induced myocardial matrix gene expression and fibrosis were also prevented by aliskiren. In vitro studies using adult rat cardiac fibroblasts also showed that aliskiren attenuated the pro-fibrotic pattern of matrix gene and protein expression induced by D,L, homocysteine. Both in vivo and in vitro studies demonstrated that the Akt pathway was activated by homocysteine, and that treatment with aliskiren attenuated Akt activation. In conclusion, aliskiren as mono-therapy has potent and direct effects on myocardial matrix turnover and beneficial effects on diastolic function.

  12. Increasing plasma parameters using sheared flow stabilization of a Z-pinch

    Science.gov (United States)

    Shumlak, U.; Nelson, B. A.; Claveau, E. L.; Forbes, E. G.; Golingo, R. P.; Hughes, M. C.; Oberto, R. J.; Ross, M. P.; Weber, T. R.

    2017-05-01

    The ZaP and ZaP-HD Flow Z-pinch experiments at the University of Washington have successfully demonstrated that sheared plasma flows can be used as a stabilization mechanism over a range of parameters that has not previously been accessible to long-lived Z-pinch configurations. The stabilization is effective even when the plasma column is compressed to small radii, producing predicted increases in magnetic field and electron temperature. The flow shear value, extent, and duration are shown to be consistent with theoretical models of the plasma viscosity, which places a design constraint on the maximum axial length of a sheared flow stabilized Z-pinch. Measurements of the magnetic field topology indicate simultaneous azimuthal symmetry and axial uniformity along the entire 100 cm length of the Z-pinch plasma. Separate control of plasma acceleration and compression has increased the accessible plasma parameters and has generated stable plasmas with radii of 0.3 cm, as measured with a high resolution digital holographic interferometer. Compressing the plasma with higher pinch currents has produced high magnetic fields (8.5 T) and electron temperatures (1 keV) with an electron density of 2 ×1017 cm-3, while maintaining plasma stability for many Alfvén times (approximately 50 μs). The results suggest that sheared flow stabilization can be applied to extend Z-pinch plasma parameters to high energy densities.

  13. Roles of the (pro)renin receptor in the kidney.

    Science.gov (United States)

    Oshima, Yoichi; Morimoto, Satoshi; Ichihara, Atsuhiro

    2014-11-06

    Prorenin receptor (PRR) is a multi-functioning protein possessing at least four different roles: (1) working as a receptor for renin and prorenin producing angiotensin I from angiotensinogen thus enhancing the tissue renin-angiotensin system; (2) inducing intracellular signals when a ligand binds to PRR; (3) participating in the functions of vacuolar proton ATPase; and (4) constituting the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology and diabetic conditions as well as recent findings regarding a soluble form of PRR are discussed. We also propose the possible mechanism concerning diabetic nephropathy as "trade-off hypothesis" from a PRR point of view. In brief, under hyperglycemic conditions, injured podocytes degrade degenerated proteins and intracellular organelles which require V-ATPase and PRR for vesicle internal acidification. Sustained hyperglycemia overproduces PRR molecules, which are transported to the transmembrane and bind to increased serum prorenin in the diabetic condition. This enhances tissue renin-angiotensin system and PRR-mediated mitogen-activated protein kinase signals, resulting in increased injurious molecules such as transforming growth factor-β, cyclooxygenase2, interleukin-1β, and tumor necrosis factor-α ending in diabetic nephropathy progression. Although many findings led us to better PRR understanding, future works should elucidate which PRR functions, of the four discussed here, are dominant in each cell and kidney disease context.

  14. Inhibition of renin activity slows down the progression of HIV-associated nephropathy.

    Science.gov (United States)

    Kumar, Dileep; Plagov, Andrei; Yadav, Iti; Torri, Deepti D; Sayeneni, Swapna; Sagar, Ankita; Rai, Partab; Adabala, Madhuri; Lederman, Rivka; Chandel, Nirupama; Ding, Guohua; Malhotra, Ashwani; Singhal, Pravin C

    2012-09-01

    In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the progression of renal lesions in two different mouse models (Vpr and Tg26) of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). In protocol A, Vpr mice were fed either water (C-VprA) or doxycycline [Doxy (D-VprA)] in their drinking water for 6 wk. In protocols B and C, Vpr mice received either normal saline (C-VprB/C), Doxy + normal saline (D-VprB/C), or Doxy + aliskiren (AD-VprB/C) for 6 wk (protocol B) or 12 wk (protocol C). In protocols D and E, Vpr mice were fed Doxy for 6 wk followed by kidney biopsy. Subsequently, half of the mice were administered either normal saline (D-VprD/E) or aliskiren (AD-VprD/E) for 4 wk (protocol D) or 8 (protocol E) wk. All D-VprA mice showed renal lesions in the form of focal segmental glomerular sclerosis and dilatation of tubules. In protocols B and C, aliskiren diminished both progression of renal lesions and proteinuria. In protocol C, aliskiren also diminished (P Doxy-treated mice displayed increased serum ANG I levels (the product of plasma renin activity); on the other hand, all aliskiren-treated mice displayed diminished serum ANG I levels. Renal tissues of D-VprC displayed increased ANG II content; however, aliskiren attenuated renal tissue ANG II production in AD-VprC. In protocol D, AD-VprD showed a 24.2% increase in the number of sclerosed glomeruli compared with 139.2% increase in sclerosed glomeruli in D-VprD (P < 0.01) from their baseline. The attenuating effect of aliskiren on the progression of renal lesions continued in AD-VprE. Aliskiren also diminished blood pressure, proteinuria, and progression of renal lesions in Tg26 mice. These findings indicate that inhibition of renin activity has a potential to slow down the progression of HIVAN.

  15. Application of atmospheric pressure plasma on polyethylene for increased prosthesis adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Van Vrekhem, S., E-mail: stijn.vanvrekhem@ugent.be [Research Unit Plasma Technology (RUPT), Department of Applied Physics, Faculty of Engineering and Architecture, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Ghent (Belgium); Cools, P. [Research Unit Plasma Technology (RUPT), Department of Applied Physics, Faculty of Engineering and Architecture, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Ghent (Belgium); Declercq, H. [Research Unit Plasma Technology (RUPT), Department of Applied Physics, Faculty of Engineering and Architecture, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Ghent (Belgium); Tissue Engineering Group, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185 6B3, 9000 Ghent (Belgium); Van Tongel, A. [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185 13K12, 9000 Ghent (Belgium); Vercruysse, C.; Cornelissen, M. [Tissue Engineering Group, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185 6B3, 9000 Ghent (Belgium); De Geyter, N.; Morent, R. [Research Unit Plasma Technology (RUPT), Department of Applied Physics, Faculty of Engineering and Architecture, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Ghent (Belgium)

    2015-12-01

    Biopolymers are often subjected to surface modification in order to improve their surface characteristics. The goal of this study is to show the use of plasma technology to enhance the adhesion of ultra-high molecular weight polyethylene (UHMWPE) shoulder prostheses. Two different plasma techniques (low pressure plasma activation and atmospheric pressure plasma polymerization) are performed on UHMWPE to increase the adhesion between (1) the polymer and polymethylmethacrylate (PMMA) bone cement and (2) the polymer and osteoblast cells. Both techniques are performed using a dielectric barrier discharge (DBD). A previous paper showed that low pressure plasma activation of UHMWPE results in the incorporation of oxygen-containing functional groups, which leads to an increased surface wettability. Atmospheric pressure plasma polymerization of methylmethacrylate (MMA) on UHMWPE results in a PMMA-like coating, which could be deposited with a high degree of control of chemical composition and layer thickness. The thin film also proved to be relatively stable upon incubation in a phosphate buffer solution (PBS). This paper discusses the next stage of the study, which includes testing the adhesion of the plasma-activated and plasma-polymerized samples to bone cement through pull-out tests and testing the cell adhesion and proliferation on the samples. In order to perform the pull-out tests, all samples were cut to standard dimensions and fixed in bone cement in a reproducible way with a sample holder specially designed for this purpose. The cell adhesion and proliferation were tested by means of an MTS assay and live/dead staining after culturing MC3T3 osteoblast cells on UHMWPE samples. The results show that both plasma activation and plasma polymerization significantly improve the adhesion to bone cement and enhance cell adhesion and proliferation. In conclusion, it can be stated that the use of plasma technology can lead to an implant with improved quality and a subsequent

  16. Elevated cAMP increases aquaporin-3 plasma membrane diffusion

    DEFF Research Database (Denmark)

    Marlar, Saw; Christensen, Eva Arnspang; Koffman, Jennifer Skaarup

    2014-01-01

    Regulated urine concentration takes place in the renal collecting duct upon arginine vasopressin (AVP) stimulation, where subapical vesicles containing aquaporin-2 (AQP2) are inserted into the apical membrane instantly increasing water reabsorption and urine concentration. The reabsorped water ex...

  17. The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production

    DEFF Research Database (Denmark)

    Tinning, Anne Robdrup; Jensen, Boye L; Schweda, Frank

    2014-01-01

    to (+/+) mice. Tissue renin concentration was higher in AQP1(-/-) mice and renin mRNA level was not different between genotypes. Mean arterial blood pressure was not different at baseline and during low salt diet but decreased significantly in both genotypes after addition of ACEI; the response was faster...

  18. PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

    Directory of Open Access Journals (Sweden)

    C Makena Hightower

    Full Text Available Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS, decreasing endothelial nitric oxide (NO production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1, a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity.

  19. Combined renin inhibition/(prorenin receptor blockade in diabetic retinopathy--a study in transgenic (mREN227 rats.

    Directory of Open Access Journals (Sweden)

    Wendy W Batenburg

    Full Text Available Dysfunction of renin-angiotensin system (RAS contributes to the pathogenesis of diabetic retinopathy (DR. Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (prorenin receptor ((PRR. Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (PRR blocker handle-region peptide (HRP on diabetic retinopathy in streptozotocin (STZ-induced diabetic transgenic (mRen227 rats (a model with high plasma prorenin levels as well as prorenin stimulated cytokine expression in cultured Müller cells. Adult (mRen227 rats were randomly divided into the following groups: (1 non-diabetic; (2 diabetic treated with vehicle; (3 diabetic treated with aliskiren (10 mg/kg per day; and (4 diabetic treated with aliskiren+HRP (1 mg/kg per day. Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen227 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen227 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Müller cells, prorenin significantly increased the expression levels of IL-1α and TNF-α, and this was completely blocked by aliskiren or HRP, their combination, (PRR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (PRR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular

  20. Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

    DEFF Research Database (Denmark)

    Brandt, Claus; Pedersen, Maria; Rinnov, Anders;

    2014-01-01

    BACKGROUND: Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation. OBJECTIVE: To elucidate the association between...... plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. STUDY DESIGN: Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS......), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans. RESULTS: Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass...

  1. Liquid chromatography-tandem mass spectrometric assay for aliskiren, a novel renin inhibitor in micro-volumes of human plasma: a pharmacokinetic application in healthy South Indian male subjects.

    Science.gov (United States)

    Adireddy, Vinayender; Pilli, Nageswara Rao; Derangula, Venkata Ramu; Satla, Shobha Rani; Ganguri, Chinna Veera Badraiah; Ponneri, Venkateswarlu

    2013-08-01

    This paper describes a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry assay for the determination of aliskiren in human plasma using nevirapine as an internal standard. Analyte and the internal standard were extracted from 100 μL of human plasma via liquid-liquid extraction using tert-butyl methyl ether. The chromatographic separation was achieved on a C18 column using a mixture of acetonitrile and 0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r(2) ≥ 0.99) over the concentration range of 0.10-1013 ng/mL. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 2.2 min for each sample made it possible to analyze a greater number of samples in a short time, thus increasing the productivity. The proposed method was found to be applicable to clinical studies.

  2. The role of direct renin inhibitors in the treatment of the hypertensive diabetic patient

    Science.gov (United States)

    2013-01-01

    Hypertensive patients with diabetes exhibit an increased risk for cardiovascular complications, such as acute coronary syndrome, stroke, heart failure and chronic kidney disease (CKD). These two chronic diseases are linked to a high rate of morbidity and mortality and for this reason it is important for the clinician to recognize the need for effective treatment of hypertension, which can require combination therapy to achieve blood pressure (BP) goals. Direct renin inhibitors (DRIs) may be useful in combination with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) as they provide a more complete blockade of the renin–angiotensin–aldosterone system (RAAS), effectively suppressing residual angiotensin II production and the counter-regulatory increase in plasma renin activity observed in patients receiving monotherapy with ACEIs or ARBs. Some questions regarding the action of aliskiren in cardiovascular and renal disorders are open. In particular, the combination therapy of aliskiren and a RAAS blocker in diabetic hypertensive patients with CKD is controversial. Several published studies demonstrated that aliskiren is suitable for once-daily administration and its antihypertensive effect is comparable or superior to that of other antihypertensive agents at recommended doses, with a good tolerability profile. At the moment the association with ACEIs and ARBs is not recommended in patients with type 2 diabetes mellitus (T2DM) and renal impairment even if a recent published open-label study of low-dose aliskiren (150 mg/daily) in association with ACEIs or ARBs has demonstrated a good tolerability profile without the adverse events found in other studies. This review provides a brief overview of RAAS blocking, in particular the rationale and clinical evidence supporting the use of the DRI aliskiren, in high-risk patients with T2DM. PMID:24143271

  3. Hyponatremia in a patient with scleroderma renal crisis: a potential role of activated renin-angiotensin system

    Directory of Open Access Journals (Sweden)

    Fukasawa Hirotaka

    2012-06-01

    Full Text Available Abstract Background Scleroderma renal crisis is an important complication of scleroderma (systemic sclerosis that is associated with significant morbidity and mortality. On the other hand, hyponatremia has never been reported in patients with scleroderma renal crisis. Case presentation A 66-year-old man with scleroderma was admitted to our hospital for an evaluation of renal dysfunction and extreme hypertension. The laboratory evaluation revealed remarkably high plasma renin activity in association with microangiopathic hemolytic anemia, and the anti-RNA polymerase III antibody assessment was positive. The patient was diagnosed with scleroderma renal crisis and was started treatment with enalapril maleate, an angiotensin-converting enzyme inhibitor. During hospitalization, the patient developed symptomatic hyponatremia three times and each laboratory analysis revealed improperly high levels of antidiuretic hormone without signs of extracellular fluid volume depletion as well as remarkably high plasma renin activities and angiotensin levels. However, hyponatremia has not been demonstrated to occur as a result of combined therapy with candesartan cilexetil, an angiotensin II receptor blocker, and aliskiren fumarate, a direct renin inhibitor. The plasma renin activities and angiotensin levels were normalized and the renal function was maintained after treatment. Conclusions To our best knowledge, this is the first documented case of scleroderma renal crisis complicated with hyponatremia. This report also suggests that the activated renin-angiotensin system may play a role in the development of hyponatremia and that hyponatremia should be taken into consideration as a rare but possible complication associated with screloderma renal crisis.

  4. The relationship between HbA(1c) and fasting plasma glucose in patients with increased plasma liver enzyme measurements

    DEFF Research Database (Denmark)

    Christiansen, R; Rasmussen, L Melholt; Nybo, H;

    2012-01-01

    levels of increased liver enzyme concentrations. Methods:  Data from 10 065 patients with simultaneous measurement of HbA(1c) , venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient...

  5. Recent advances in tissue (pro)renin imaging.

    Science.gov (United States)

    Prokai, Agnes; Peti-Peterdi, Janos

    2010-06-01

    Due to its pivotal role in blood pressure control and renal pathologies there is renewed interest in renin and its precursor prorenin. Also, the newly discovered (pro)renin receptor is a new element of the ever broadening renin-angiotensin system (RAS). The complexity of RAS including the recently recognized collecting duct site of (pro)renin (a term denoting both renin and prorenin) synthesis requires the use of advanced research techniques such as multiphoton fluorescence microscopy. With the help of this technology we have pioneered an imaging approach to directly visualize (pro)renin content, release and tissue activity in the living kidney. The use of this technology is reviewed here and exemplified by the direct visualization of (pro)renin activity in the collecting duct. New pharmacological tools, the renin inhibitor aliskiren and the handle region peptide (decoy peptide) was used to further characterize the intra-renal, collecting duct RAS.

  6. Anxiety-induced plasma norepinephrine augmentation increases reactive oxygen species formation by monocytes in essential hypertension.

    Science.gov (United States)

    Yasunari, Kenichi; Matsui, Tokuzo; Maeda, Kensaku; Nakamura, Munehiro; Watanabe, Takanori; Kiriike, Nobuo

    2006-06-01

    An association between anxiety and depression and increased blood pressure (BP) and cardiovascular disease risk has not been firmly established. We examined the hypothesis that anxiety and depression lead to increased plasma catecholamines and to production of reactive oxygen species (ROS) by mononuclear cells (MNC) in hypertensive individuals. We also studied the role of BP in this effect. In Protocol 1, a cross-sectional study was performed in 146 hypertensive patients to evaluate whether anxiety and depression affect BP and ROS formation by MNC through increasing plasma catecholamines. In Protocol 2, a 6-month randomized controlled trial using a subtherapeutic dose of the alpha(1)-adrenergic receptor antagonist doxazosin (1 mg/day) versus placebo in 86 patients with essential hypertension was performed to determine whether the increase in ROS formation by MNC was independent of BP. In Protocol 1, a significant relationship was observed between the following: trait anxiety and plasma norepinephrine (r = 0.32, P < .01); plasma norepinephrine and ROS formation by MNC (r = 0.36, P < .01); and plasma norepinephrine and systolic, diastolic, and mean BP (r = 0.17, P = .04; r = 0.26, P = .02; r = 0.23, P < .01, respectively). In Protocol 2, subtherapeutic doxazosin treatment (1 mg/day) had no significant effect on BP. However doxazosin significantly decreased ROS formation by MNC compared with placebo (P < .01). Trait anxiety may increase plasma norepinephrine and increase ROS formation by MNC independent of BP in hypertensive patients.

  7. Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

    Science.gov (United States)

    Dembek, K A; Onasch, K; Hurcombe, S D A; MacGillivray, K C; Slovis, N M; Barr, B S; Reed, S M; Toribio, R E

    2013-01-01

    The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  8. Low LBNP Tolerance in Men is Associated With Attenuated Activation of Renin-Angiotensin System

    Science.gov (United States)

    Greenleaf, John E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N.-J.; Warberg, J.; Videbaeck, R.; Simonson, S. R.; Norsk, P.; Dalton, Bonnie P. (Technical Monitor)

    1999-01-01

    Vasoactive hormone concentrations (epinephrine (pE), norepinephrine (pNE), angiotensin II (pATII), vasopressin (pVP), endothelin 1 (pET1)] and plasma renin activity (pRA) were measured during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the reninangiotensin system is related to LBNP tolerance. Healthy men (2,822 cal per day, 2 mmol per kilogram per day Na (+)) were exposed to 30 min of progressive LBNP to -50mmHg. LBNP was uneventful for 7 men (2512 yr, HiTol group), but 8 men (26 plus or minus 3 yr) reached pre-syncope after 11 plus or minus 1 min (P less than 0.001, LoTol group). Mean arterial pressure was unchanged. Central venous pressure and left atrial diameter decreased in both groups (5-6 mmHg by 30%, P less than 0.05). Control [hormone] were similar but, pRA differed between groups (LoTol 0.6 plus or minus 0.1, HiTol 1.2 plus or minus 0.1 ng Ang1 per milliliter per hour, per hour, P less than 0.05). LBNP increased (P less than 0.05) pRA and pATII more in HiTol (9.9 plus or minus 2.2 ng Ang1 per milliliter per hour and 58 plus or minus 12 pg per milliliter) than LoTol (4.3 plus or minus 0.9 ng Angl per milliliter per hour and 28 plus or minus 6 pg per milliliter). In contrast, pVP was higher (P less than 0.05) in LoTol than in HiTol. The response of the renin-angiotensin system seems linked to the occurrence of pre-syncope, and measurement of resting pRA may be predictive.

  9. 应用ROC曲线评价醛固酮肾素比值对原发性醛固酮增多症诊断的临床意义%Significance of aldosterone/plasma renin activity ratio in diagnosis of primary aldosteronism with ROC curve

    Institute of Scientific and Technical Information of China (English)

    邓西元; 庞欣欣; 张旭

    2011-01-01

    目的 应用接受者操作特性曲线(ROC曲线)选择术前诊断原发醛固酮增多症(原醛症)的醛固酮肾素比值(ARR)的最佳切点,并探讨醛固酮肾素比值在诊断原醛症方面的临床意义.方法 从2004年1月到2007年6月在同济医院行手术治疗的肾上腺肿瘤病例133例分为总原醛症组、醛固酮瘤组、肾上腺增生组和非原醛组,用ROC工作曲线选择醛固酮肾素比值的最佳切点.结果 总原醛症组和醛固酮瘤组的醛固酮肾素比值的最佳切点为40,而肾上腺增生组的最佳切点为20,醛固酮肾素比值与肾素活性(r=0.615,P<0.01)和血管紧张素Ⅱ(r=0.527,P<0.01)有负相关性.结论 运用醛固酮肾素比值来诊断原醛有很大价值,但还存在不足.%Objective To choose the best cut-off value and to evaluate the clinical significance of aldosterone/plasma renin activity ratio(ARR) for preoperative diagnosis of primary aldosteronism by ROC curve. Methods Data of 133 adrenal tumor cases treated surgically at Tongji Hospital from Jan. 2004 to June 2007 were retrospectively analyzed. The cases were divided into total primary aldosteronism group, APA group, adrenal hyperplasia group and non- primary aldosteronism group,and the best out-off value of ARR was detected by ROC. Results The best cut-off value of ARR was 40 in the total primary aldosteronism group and APA group, and was 20 in the adrenal hyperplasia group. The cut-off value of ARR was negatively correlated with plasma renin activity ratio( r= -0. 615 P<0. 01) and Angiotensin Ⅱ ( r= -0. 527 P<0.01) . Conclusions The use of ARR for diagnosis of primary aldosteronism is significant although it's not perfect.

  10. On the origin of urinary renin: A translational approach

    NARCIS (Netherlands)

    L.C.W. Roksnoer (Lodi); Heijnen, B.F.J. (Bart F.J.); Nakano, D. (Daisuke); Peti-Peterdi, J. (Janos); S.B. Walsh (Stephen); I.M. Garrelds (Ingrid); J.M. van Gool (Jeanette); R. Zietse (Bob); H.A.J. Struijker Boudier (Harry A.); E.J. Hoorn (Ewout); A.H.J. Danser (Jan)

    2016-01-01

    textabstractUrinary angiotensinogen excretion parallels albumin excretion, which is not the case for renin, while renin's precursor, prorenin, is undetectable in urine. We hypothesized that renin and prorenin, given their smaller size, are filtered through the glomerulus in larger amounts than album

  11. Targeted deletion of murine CEACAM 1 activates PI3K-Akt signaling and contributes to the expression of (Pro)renin receptor via CREB family and NF-κB transcription factors.

    Science.gov (United States)

    Huang, Jiqian; Ledford, Kelly J; Pitkin, William B; Russo, Lucia; Najjar, Sonia M; Siragy, Helmy M

    2013-08-01

    The carcinoembryonic antigen-related cell adhesion molecule 1 regulates insulin sensitivity by promoting hepatic insulin clearance. Mice bearing a null mutation of Ceacam1 gene (Cc1(-/-)) develop impaired insulin clearance followed by hyperinsulinemia and insulin resistance, in addition to visceral obesity and increased plasma fatty acids. Because insulin resistance is associated with increased blood pressure, we investigated whether they develop higher blood pressure with activated renal renin-angiotensin system and whether this is mediated, in part, by the upregulation of renal (pro)renin receptor (PRR) expression. Compared with age-matched wild-type littermates, Cc1(-/-) mice exhibited increased blood pressure with increased activation of renal renin-angiotensin systems and renal PRR expression. Cytoplasmic and nuclear immunostaining of phospho-PI3K p85α and phospho-Akt was enhanced in the kidney of Cc1(-/-) mice. In murine renal inner medullary collecting duct epithelial cells with lentiviral-mediated small hairpin RNA knockdown of carcinoembryonic antigen-related cell adhesion molecule 1, PRR expression was upregulated and phosphorylation of PI3K (Tyr508), Akt (Ser473), NF-κB p65 (Ser276), cAMP response element-binding protein/activated transcription factor (ATF)-1 (Ser133), and ATF-2 (Thr71) was enhanced. Inhibiting PI3K with LY294002 or Akt with Akt inhibitor VIII attenuated PRR expression. In conclusion, global null deletion of Ceacam1 caused an increase in blood pressure with increased renin-angiotensin system activation together with upregulation of PRR via PI3K-Akt activation of cAMP response element-binding protein 1, ATF-1, ATF-2, and NF-κB p65 transcription factors.

  12. Effects of Acute Exposure to Increased Plasma Branched-Chain Amino Acid Concentrations on Insulin-Mediated Plasma Glucose Turnover in Healthy Young Subjects

    OpenAIRE

    Sarah Everman; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

    2015-01-01

    Background Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. Objective To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Methods Ten healthy subjects were randomly assigned to...

  13. Increased plasma free fatty acid and triglyceride levels after single administation of toluene in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Setsunori; Tanabe, Koichi; Shiono, Hiroshi (Shimane Medical Univ., Izumo (Japan)); Maseda, Chikatoshi (Shimane Prefectural Police Headquarters, Matsue (Japan)); Fukui, Yuko (Kyoto Univ. (Japan))

    1988-01-01

    Changes of plasma lipids (triglyceride, TG: total cholesterol, Cho; and phospholipids, PL), free fatty acid (FFA), and blood glucose (BG) were studied in male rabbits after toluene administration (0.5 g/kg per os). Hypertriglyceridemia was observed at and after 2 h. Plasma FFA and BG were elevated temporarily during the early stage and lowered gradually thereafter. Initially, plasma Cho and PL were virtually unchanged, by the Cho levels increased slowly after 6 h. The hypertriglyceridemia observed may have some adverse effects on heart function.

  14. Increased plasma carnitine in trauma patients given lipid-supplemented total parenteral nutrition.

    Science.gov (United States)

    Davis, A T; Albrecht, R M; Scholten, D J; Morgan, R E

    1988-12-01

    The purpose of this study was to determine the effects of altering the fuel substrate mix of total parenteral nutrition (TPN) on plasma and urinary carnitine in trauma patients. TPN solutions were either 100% carbohydrate (CHO) based or lipid based (70% CHO, 30% lipid). There were statistically significant (p less than 0.05) increases in plasma levels of free carnitine, short-chain acyl carnitine, and total carnitine in trauma patients receiving lipid-based TPN. No significant differences in urinary carnitine excretion were noted between groups. We conclude that the use of lipids in the TPN of trauma patients leads to an alteration in plasma carnitine metabolism.

  15. Higher plasma prorenin concentration plays a role in the development of coronary artery disease

    OpenAIRE

    Yoshida, Gakuro; Kawasaki, Masanori; MURATA, Ichijiro; Hayakawa, Yuka; AOYAMA, Takuma; Miyazaki, Nagisa; Yamada, Yoshihisa; NISHIGAKI, Kazuhiko; Arai, Yoshie; Suzuki, Fumiaki; Minatoguchi, Shinya

    2015-01-01

    Background Prorenin and renin are both involved in atherosclerosis. However, the role of plasma prorenin and renin in the development and progression of coronary artery disease (CAD) is still not clear. Thus, we aimed to examine the relationships among plasma prorenin concentration, CAD and clinical parameters. Methods We measured plasma prorenin and renin concentrations and other parameters in 85 patients who underwent coronary angiography. Patients were divided into a CAD group (≥75 % steno...

  16. Aliskiren inhibits the renin-angiotensin system in retinal pigment epithelium cells.

    Science.gov (United States)

    Simão, Sónia; Santos, Daniela F; Silva, Gabriela A

    2016-09-20

    Observations of increased angiotensin II levels and activation of the (pro)renin receptor in retinopathies support the role of ocular renin-angiotensin system (RAS) in the development of retinal diseases. While targeting RAS presents significant therapeutic potential, current RAS-based therapies are ineffective halting the progression of these diseases. A new class of drugs, the direct renin inhibitors such as aliskiren, is a potential therapeutic alternative. However, it is unclear how aliskiren acts in the retina, in particular in the retinal pigment epithelium (RPE), the structure responsible for the maintenance of retinal homeostasis whose role is deeply compromised in retinal diseases. We firstly analyzed the expression and activity of the main RAS components in RPE cells. Time- and concentration-dependent treatments with aliskiren were performed to modulate different pathways of the RAS in RPE cells. Our data demonstrate that RPE cells express the main RAS constituents. Exposure of RPE cells to aliskiren inhibited the activity of renin and consequently decreased the levels of angiotensin II. Additionally, aliskiren reduced the translocation of the (pro)renin receptor to the cellular membrane of RPE cells preventing the activation of ERK1/2. Our findings of the RPE well-defined RAS, together with the demonstration that aliskiren effectively blocks this system at different steps of the cascade, suggest that aliskiren might be an alternative and successful drug in preventing the deleterious effects derived from the overactivation of the RAS, known to contribute to the pathogenesis of different retinal diseases.

  17. Increase in plasma lipid peroxide in cats fed a fish diet.

    Science.gov (United States)

    Momoi, Y; Goto, Y; Tanide, K; Takahashi, N; Watari, T; Yamazo, K; Tsujimoto, H; Kudo, T

    2001-12-01

    Plasma lipid peroxide levels were examined in cats. Plasma lipid peroxide levels in 3 of 4 clinical cases which had been fed raw fish were higher than those in normal cats. When healthy cats were put on a raw fish diet in controlled conditions, a remarkable increase in plasma lipid peroxide was observed. This increase occurred within 1 to 3 weeks in cats without obvious clinical disorders. We also showed that a continuous raw fish diet is necessary to cause the increase, but the increase was transient and restored in spite of a continuous raw fish diet, indicating the development of an unidentified antioxidant process. Our results clearly indicate that intake of foods high in polyunsaturated fatty acid can induce oxidative stress in cats.

  18. A Sulfur Amino Acid–Free Meal Increases Plasma Lipids in Humans123

    Science.gov (United States)

    Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei; Strobel, Fred; Gletsu-Miller, Nana; Accardi, Carolyn J.; Lee, Kichun S.; Wu, Shaoxiong; Ziegler, Thomas R.; Jones, Dean P.

    2011-01-01

    The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR (1H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (18–36 y, 5 males and 3 females) were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (depletion), and then fed isoenergetic, isonitrogenous meals containing 56 mg·kg−1·d−1 SAA for 4.5 d (repletion). On the first and last day of consuming the chemically defined meals, a morning meal containing 60% of the daily food intake was given and plasma samples were collected over an 8-h postprandial time course for characterization of metabolic changes by 1H-NMR spectroscopy. SAA-free food increased peak intensity in the plasma 1H-NMR spectra in the postprandial period. Orthogonal signal correction/partial least squares-discriminant analysis showed changes in signals associated with lipids, some amino acids, and lactate, with notable increases in plasma lipid signals (TG, unsaturated lipid, cholesterol). Conventional lipid analyses confirmed higher plasma TG and showed an increase in plasma concentration of the lipoprotein lipase inhibitor, apoC-III. The results show that plasma 1H-NMR spectra can provide useful macronutrient profiling following a meal challenge protocol and that a single meal with imbalanced SAA content alters postprandial lipid metabolism. PMID:21677075

  19. Changes of plasma concentrations in renin system and some vasoactive peptides in aged hypertension patients%老年高血压病患者肾素系统和血管活性肽的变化

    Institute of Scientific and Technical Information of China (English)

    李红梅; 叶季鲜; 李敏; 田丽君; 高延; 高群; 李丽辉

    2001-01-01

    目的:探讨老年原发性高血压(EH)患者肾素(RA)-血管紧张素(AT)-醛固酮(ALD)系统(RAAS)及心房钠尿肽(ANP)、内皮素(ET)、降钙素基因相关肽(CGRP)等血管活性肽的变化。方法:放射免疫方法检测96例健康老年人和104例老年EH患者血浆肾素活性(PRA),ATⅡ,ALD,ANP,ET,CGRP浓度。结果:①两组PRA,ATⅡ,ALD浓度均随年龄增长而降低(P0.05);老年EH患者血浆ANP,ET浓度随年龄增长而明显增高(P0.05);the plasma concentrations of ANP and ET in hypertension patients were apparently increased with age (P<0.05 or P<0.01), and that of CGRP was decreased (P<0.01);the plasma concentrations of ANP and ET in different age groups of hypertension patients were significantly higher than those of the normal control (P<0.05 or P<0.01) and those of CGRP were lower than those of the normal controls (P<0.05 or P<0.01). There was a positive correlation between ATⅡ and ANP,as well as between ATⅡ and ET (r=0.60,0.79,P<0.01) and there was a negative correlation between ATⅡ and CGRP (r=-0.59,P<0.01) in hypertension patients. CONCLUSION:In physiolgoical state,the action of traditional RAAS on blood pressure might be decreased with age in aged people,and the vasoactive peptides (ANP,ET,CGRP) might contribute more to the cardiovascular action to keep blood pressure stable. Activity of vasoconstrictive peptides(ATⅡ,ET) were incresaed and activity of vasodilative peptide(CGRP) was decreased.

  20. PGE2 upregulates renin through E-prostanoid receptor 1 via PKC/cAMP/CREB pathway in M-1 Cells.

    Science.gov (United States)

    Gonzalez, Alexis A; Salinas-Parra, Nicolas; Leach, Dan; Navar, L Gabriel; Prieto, Minolfa C

    2017-07-12

    During the early phase of angiotensin (ANG) II-dependent hypertension tubular prostaglandin E2 (PGE2) is increased. Renin synthesis and secretion in the collecting duct (CD) is upregulated by ANGII contributing to further intratubular ANGII formation. However, what happens first and whether the triggering mechanism is independent of tubular ANGII, remain unknown. PGE2 stimulates renin synthesis in juxtaglomerular (JG) cells via E-prostanoid (EP) receptors through cAMP/CREB pathway. EP receptors are also expressed in the CD. Here, we tested the hypothesis that renin is upregulated by PGE2 in CD cells. M-1 CD cell line expressed EP1, EP3 and EP4 but not EP2. Dose response experiments in the presence of AT1 receptor blockade with candesartan demonstrated that 10-6 M PGE2 maximally increases renin mRNA (~4 fold) and prorenin/renin protein levels (~2 fold). This response was prevented by micromolar doses of SC-19220 (EP1 antagonist), attenuated by the EP4 antagonist, L-161,982, and exacerbated by the highly selective EP3 antagonist, L-798106 (~10 fold increase). To further evaluate the signaling pathway involved we used the PKC inhibitor calphostin C and transfections with PKCα dominant negative (DN). Both strategies blunted the PGE2-induced increases in cAMP levels, CREB phosphorylation and augmentation of renin. Knockdown of EP1 receptor and CREB also prevented renin upregulation. These results indicate that PGE2 increases CD renin expression through EP1 receptor via PKC/cAMP/CREB pathway. Therefore, we conclude that during early stages of ANGII-dependent hypertension, there is augmentation of PGE2 that stimulates renin in the CD, resulting in increased tubular ANGII formation and further stimulation of renin. Copyright © 2017, American Journal of Physiology-Renal Physiology.

  1. The Renal Renin-Angiotensin System

    Science.gov (United States)

    Harrison-Bernard, Lisa M.

    2009-01-01

    The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

  2. An ectopic renin-secreting adrenal corticoadenoma in a child with malignant hypertension.

    Science.gov (United States)

    Kaslow, Abraham M; Riquier-Brison, Anne; Peti-Peterdi, Janos; Shillingford, Nick; HaDuong, Josephine; Venkatramani, Rajkumar; Gayer, Christopher P

    2016-03-01

    A previously healthy 7-year-old male presented with hypertensive emergency, hypokalemia, and elevated plasma renin activity and aldosterone levels. There was no evidence of virilization or cushingoid features. MRI of the abdomen revealed a large (5 × 5 × 3 cm) peripherally enhancing, heterogeneous mass arising from the left adrenal gland. The patient was treated for a suspected pheochromocytoma. However, his blood pressure was not responsive to alpha-blockade. Blood pressure was controlled with a calcium channel blocker and an angiotensin-converting enzyme (ACE) inhibitor. A complete surgical resection of the mass was performed. Postoperatively, his blood pressure normalized and he did not require antihypertensives. On pathological examination, the tumor tissue stained negative for chromogranin and positive for renin. The final diagnosis was renin-secreting adrenal corticoadenoma, an extremely rare adrenal tumor not previously reported in a pediatric patient. Malignant hypertension due to a renin-secreting tumor may need to be distinguished from a pheochromocytoma if alpha-adrenergic blockade is ineffective.

  3. Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

    Science.gov (United States)

    McVicar, M; Carman, C; Chandra, M; Abbi, R J; Teichberg, S; Kahn, E

    1993-08-01

    A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following: 1. Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female. 2. Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism. 3. Renal angiography was initially negative in more than half the cases. 4. Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases. 5. Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative. 6. Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

  4. Imaging renin content and release in the living kidney.

    Science.gov (United States)

    Toma, Ildikó; Kang, Jung Julie; Peti-Peterdi, János

    2006-01-01

    Renin release is the first, and at least initially, the rate-limiting step in the activation of the renin-angiotensin system, which helps to maintain body salt and water balance. Recent advances in our understanding of pathophysiology have generated a renewed interest in the multiple roles of renin and prorenin as a hormone, enzyme, and signaling molecule. The assays available to measure renin content, release and tissue activity are complex, indirect and work with significant internal errors. We developed an imaging approach to directly visualize renin content and study the dynamics of both the release and tissue activity of renin. Our experimental model uses multiphoton fluorescence microscopy, which is ideal for deep optical sectioning of the living renal tissue. Here we review the application of this renin imaging approach to the dissected, in vitro microperfused glomerulus as well as in the intact kidney in vivo.

  5. Increased FGF21 plasma levels in humans with sepsis and SIRS.

    Science.gov (United States)

    Gariani, Karim; Drifte, Geneviève; Dunn-Siegrist, Irène; Pugin, Jérôme; Jornayvaz, François R

    2013-01-01

    Fibroblast growth factor 21 (FGF21) is a key regulator in glucose and lipid metabolism and its plasma levels have been shown to be increased not only in humans in different situations such as type 2 diabetes, obesity, and nonalcoholic fatty liver disease but also in animal models of sepsis and pancreatitis. FGF21 is considered as a pharmacological candidate in conditions associated with insulin resistance. The aim of this study was to compare FGF21 plasma levels in patients with sepsis, in patients with systemic inflammatory response syndrome (SIRS), and in healthy controls. We measured FGF21 plasma concentrations in 22 patients with established sepsis, in 11 with SIRS, and in 12 healthy volunteers. Here, we show that FGF21 levels were significantly higher in plasma obtained from patients with sepsis and SIRS in comparison with healthy controls. Also, FGF21 levels were significantly higher in patients with sepsis than in those with noninfectious SIRS. FGF21 plasma levels measured at study entry correlated positively with the APACHE II score, but not with procalcitonin levels, nor with C-reactive protein, classical markers of sepsis. Plasma concentrations of FGF21 peaked near the onset of shock and rapidly decreased with clinical improvement. Taken together, these results indicate that circulating levels of FGF21 are increased in patients presenting with sepsis and SIRS, and suggest a role for FGF21 in inflammation. Further studies are needed to explore the potential role of FGF21 in sepsis as a potential therapeutic target.

  6. Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor.

    Science.gov (United States)

    Ortiz-Capisano, M Cecilia; Reddy, Mahendranath; Mendez, Mariela; Garvin, Jeffrey L; Beierwaltes, William H

    2013-02-01

    The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal juxtaglomerular (JG) cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin release. The postreceptor pathway for the CaSR in JG cells is unknown. In parathyroids, CaSR acts through G(q) and/or G(i). Activation of G(q) stimulates phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP(3)), releasing calcium from intracellular stores. G(i) stimulation inhibits cAMP formation. In afferent arterioles, the ryanodine receptor (RyR) enhances release of stored calcium. We hypothesized JG cell CaSR activation inhibits renin via the PLC/IP(3) and also RyR activation, increasing intracellular calcium, suppressing cAMP formation, and inhibiting renin release. Renin release from primary cultures of isolated mouse JG cells (n = 10) was measured. The CaSR agonist cinacalcet decreased renin release 56 ± 7% of control (P PLC inhibitor U73122 reversed cinacalcet inhibition of renin (104 ± 11% of control). The IP(3) inhibitor 2-APB also reversed inhibition of renin from 56 ± 6 to 104 ± 11% of control (P PLC/IP(3) pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition.

  7. Disturbed B cell subpopulations and increased plasma cells in myasthenia gravis patients.

    Science.gov (United States)

    Kohler, Siegfried; Keil, Thomas Oskar Philipp; Swierzy, Marc; Hoffmann, Sarah; Schaffert, Hanne; Ismail, Mahmoud; Rückert, Jens Carsten; Alexander, Tobias; Hiepe, Falk; Gross, Christian; Thiel, Andreas; Meisel, Andreas

    2013-11-15

    Whether there is a general perturbation of B and plasma cell subsets in myasthenia gravis (MG) has not been investigated so far. Here we performed a detailed flow cytometric analysis of blood and if available thymic tissue in order to detect MG-specific and therapy-induced changes. We observed significant differences in the distribution of B cell subsets in MG patients, yet these were mainly attributable to medical treatment. Furthermore MG is associated with significantly increased frequencies of plasma cells that were especially activated in purely ocular disease manifestation. In contrast to thymoma, B cell subset distribution in hyperplastic thymus could be distinguished from peripheral blood, however both tissues were not significantly enriched with plasma cells. Thus B cell differentiation in general is not defective in MG, but modified by therapy and enhanced frequencies of plasma cells can be detected in MG patients.

  8. Enhanced toroidal flow stabilization of edge localized modes with increased plasma density

    Science.gov (United States)

    Cheng, Shikui; Zhu, Ping; Banerjee, Debabrata

    2017-09-01

    Toroidal flow alone is generally thought to have an important influence on tokamak edge pedestal stability, even though theoretical analysis often predicts merely a weak stabilizing effect of toroidal flow on the edge localized modes (ELMs) in experimental parameter regimes. For the first time, we find from two-fluid MHD calculations that such a stabilization, however, can be significantly enhanced by increasing the edge plasma density. Our finding resolves a long-standing mystery whether or how toroidal rotation can indeed have an effective influence on ELMs, and explains why the ELM mitigation and suppression by toroidal rotation are more favorably achieved in higher collisionality regime in recent experiments. The finding suggests a new control scheme on modulating toroidal flow stabilization of ELMs with plasma density, along with a new additional constraint on the optimal level of plasma density for the desired edge plasma conditions.

  9. Reduced Expression of the Extracellular Calcium-Sensing Receptor (CaSR Is Associated with Activation of the Renin-Angiotensin System (RAS to Promote Vascular Remodeling in the Pathogenesis of Essential Hypertension.

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Qu

    Full Text Available The proliferation of vascular smooth muscle cells (VSMCs, remodeling of the vasculature, and the renin-angiotensin system (RAS play important roles in the development of essential hypertension (EH, which is defined as high blood pressure (BP in which secondary causes, such as renovascular disease, are absent. The calcium-sensing receptor (CaSR is involved in the regulation of BP. However, the underlying mechanisms by which the CaSR regulates BP are poorly understood. In the present study, the role of the CaSR in EH was investigated using male spontaneously hypertensive rats (SHRs and rat and human plasma samples. The percentages of medial wall thickness to external diameter (WT%, total vessel wall cross-sectional area to the total area (WA% of thoracic arteries, as well as the percentage of wall area occupied by collagen to total vessel wall area (CA% were determined. Tissue protein expression and plasma concentrations of the CaSR, cyclic adenosine monophosphate (cAMP, renin, and angiotensin II (Ang II were additionally assessed. WT%, WA%, and CA% were found to increase with increasing BP, whereas the plasma concentration of CaSR was found to decrease. With increasing BP, the levels of smooth muscle actin and calponin decreased, whereas those of osteopontin and proliferating cell nuclear antigen increased. The CaSR level negatively correlated with the levels of cAMP and Ang II, but positively correlated with those of renin. Our data suggest that reduced expression of the CaSR is correlated with activation of the RAS, which induces increased vascular remodeling and VSMC proliferation, and thereby associated with EH in the SHR model and in the Han Chinese population. Our findings provide new insights into the pathogenesis of EH.

  10. The Renin-Angiotensin System Modulates Inflammatory Processes in Atherosclerosis: Evidence from Basic Research and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Fabrizio Montecucco

    2009-01-01

    Full Text Available Recent evidence shows that the renin-angiotensin system is a crucial player in atherosclerotic processes. The regulation of arterial blood pressure was considered from its first description of the main mechanism involved. Vasoconstriction (mediated by angiotensin II and salt and water retention (mainly due to aldosterone were classically considered as pivotal proatherosclerotic activities. However, basic research and animal studies strongly support angiotensin II as a proinflammatory mediator, which directly induces atherosclerotic plaque development and heart remodeling. Furthermore, angiotensin II induces proatherosclerotic cytokine and chemokine secretion and increases endothelial dysfunction. Accordingly, the pharmacological inhibition of the renin-angiotensin system improves prognosis of patients with cardiovascular disease even in settings of normal baseline blood pressure. In the present review, we focused on angiotensin-convertingenzyme (ACE inhibitors, angiotensin II receptor blockers (ARBs, and renin inhibitors to update the direct activities of the renin-angiotensin system in inflammatory processes governing atherosclerosis.

  11. Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system

    Science.gov (United States)

    Greenleaf, J. E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N. J.; Warberg, J.; Videbaek, R.; Simonson, S. R.; Norsk, P.

    2000-01-01

    Plasma vasoactive hormone concentrations [epinephrine (p(Epi)), norepinephrine (p(NE)), ANG II (p(ANG II)), vasopressin (p(VP)), endothelin-1 (p(ET-1))] and plasma renin activity (p(RA)) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol. kg(-1). day(-1) Na(+)) were exposed to 30 min of LBNP from -15 to -50 mmHg. LBNP was uneventful for seven men [25 +/- 2 yr, high-tolerance (HiTol) group], but eight men (26 +/- 3 yr) reached presyncope after 11 +/- 1 min [P concentrations were similar between groups, however, p(RA) differed between them (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng ANG I. ml(-1). h(-1), P < 0.05). LBNP increased (P < 0. 05) p(RA) and p(ANG II), respectively, more in the HiTol group (9.9 +/- 2.2 ng ANG I. ml(-1). h(-1) and 58 +/- 12 pg/ml) than in LoTol subjects (4.3 +/- 0.9 ng ANG I. ml(-1). h(-1) and 28 +/- 6 pg/ml). In contrast, the increase in p(VP) was higher (P < 0.05) in the LoTol than in the HiTol group. The increases (P < 0.05) for p(NE) were nonsignificant between groups, and p(ET-1) remained unchanged. Thus there may be a causal relationship between attenuated activation of p(RA) and p(ANG II) and presyncope, with p(VP) being a possible cofactor. Measurement of resting p(RA) may be of predictive value for those with lower hypotensive tolerance.

  12. Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model.

    Science.gov (United States)

    Narita, Yuki; Ueda, Miki; Uchimura, Kohei; Kakizoe, Yutaka; Miyasato, Yoshikazu; Mizumoto, Teruhiko; Morinaga, Jun; Hayata, Manabu; Nakagawa, Terumasa; Adachi, Masataka; Miyoshi, Taku; Sakai, Yoshiki; Kadowaki, Daisuke; Hirata, Sumio; Mukoyama, Masashi; Kitamura, Kenichiro

    2016-02-01

    We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin-aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.

  13. [Cardiovascular effects of peptide inhibitors of the renin-substrate reaction in rats with renovascular hypertension. Goldblatt: 2 kidneys--1 clip].

    Science.gov (United States)

    Labbé, T; Bonoron-Adèle, S; Geoffre, S; Précigoux, G; Laval, M; Hospital, M; Besse, P

    1988-06-01

    The antihypertensive effects of 2 different peptidic substrate analogs: AG 84-10 AG 85-12 were investigated in renovascular hypertensive (Goldblatt, 2 kidneys--1 clip) Sprague-Dawley male rats. AG 84-10 (Ac-Pro-Phe-His-Leu-Val-Tyr) is similar to Angiotensinogen 6-13 and AG 85-12 (Ac-Ile-His-Pro-Phe-His-Leu) mimics the C-terminal portion of Angiotensin I. 6 weeks after clipping, hemodynamic profiles of these molecules [Heart rate (HR), mean arterial pressure (MAP), filling parameters, peripheral vascular resistances (PR) and cardiac output (CO)] during 90 minutes, were determined in the anesthetized animals. CO was measured using a thermodilution technique. Parallel radio-immunologic dosages of plasma renin activity were performed. Measurements and calculation of previously defined hemodynamic variables, every 10 minutes, demonstrated that: AG 84-10 exerted an early but transient decrease of MAP and PR, an increase of CO without modification of other hemodynamic parameters. AG 85-12 induced a late and durable decrease of MAP and PR with a significant decrease of heart rate, but without modification of CO and other hemodynamic variables. Example: PR mmHg/ml/mn/kg (mean +/- SD): *p less than 0.05 ** p less than 0.01. (Table: see text). The different levels of plasma renin activity were in accordance with hemodynamic data. So, the 2 peptidic substrate analogs elicited antihypertensive effects with a more efficient action of AG 85-12.

  14. Renin-angiotensin system activity in vitamin D deficient, obese individuals with hypertension: An urban Indian study

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    Sunil Kumar Kota

    2011-01-01

    Full Text Available Background: Elevated renin-angiotensin-aldosterone system (RAAS activity is an important mechanism in the development of hypertension. Both obesity and 25-hydroxy vitamin D [25(OHD] deficiency have been associated with hypertension and augmented renin-angiotensin system (RAS activity. We tried to test the hypothesis that vitamin D deficiency and obesity are associated with increased RAS activity in Indian patients with hypertension. Materials and Methods: Fifty newly detected hypertensive patients were screened. Patients with secondary hypertension, chronic kidney disease, or coronary artery disease were excluded. Patients underwent measurement of vitamin D and plasma renin and plasma aldosterone concentrations. They were divided into three groups according to their baseline body mass index (BMI; normal <25 kg/m 2 , overweight 25-29.9 kg/m 2 and obese ≥30 kg/m 2 and 25(OHD levels (deficient <20 ng/ml, insufficient 20-29 ng/ml and optimal ≥30 ng/ml. Results: A total of 50 (male:female = 32:18 patients were included, with a mean age of 49.5 ± 7.8 years, mean BMI of 28.3 ± 3.4 kg/m 2 and a mean 25(OHD concentration of 18.5 ± 6.4 ng/ml. Mean systolic blood pressure (SBP was 162.4 ± 20.2 mm Hg and mean diastolic blood pressure (DBP was 100.2 ± 11.2 mm Hg. All the three blood pressure parameters [SBP, DBP and mean arterial pressure (MAP] were significantly higher among individuals with lower 25(OHD levels. The P values for trends in SBP, DBP and MAP were 0.009, 0.01 and 0.007, respectively. Though all the three blood pressure parameters (SBP, DBP and MAP were higher among individuals with higher BMIs, they were not achieving statistical significance. Increasing trends in PRA and PAC were noticed with lower 25(OHD and higher BMI levels. Conclusion: Vitamin D deficiency and obesity are associated with stimulation of RAAS activity. Vitamin D supplementation along with weight loss may be studied as a therapeutic strategy to reduce tissue RAS

  15. Value of combination strategy based on plasma aldosterone/renin concentration ratio in screening of primary aldosteronism%基于血浆醛固酮/肾素浓度比的联合策略在原发性醛固酮增多症中的筛查价值

    Institute of Scientific and Technical Information of China (English)

    孙明芳; 杨珊; 何小群; 周波; 李启富; 段雅倩

    2015-01-01

    Objective To explore the best way for clinical screening of primary aldosteronism (PA).Methods Three hundred and three suspected cases of PA were collected and divided into groups of primary aldosteronism group, essential hypertension group, and nonsecreting cortical adrenal tumor group.The plasma aldosterone concentration/plasma renin concentration ratio ( ARR) was used to draw the receiver operating characteristic ( ROC) curve and obtain the best cut-off point.Furthermore, the current screening schemes for PA were compared.Results Upright ARR yield had larger areas under the ROC curve than plasma aldosterone concentration or plasma renin concentration under all conditions of testing. The best cut-off point of upright ARR[(pg/ml)/(μIU/ml)] for the diagnosis of PA was 43.45.During the two postural stimulation tests,the two upright ARR exceeded 43.45 with the highest diagnostic sensitivity of PA reaching 0.94.During the two upright tests ARR was less than 43.45, with a sensitivity of 0.74, and a specificity of 0.94.Conclusion To screen for PA in high-risk populations, twice postural stimulation test is recommended.As long as the upright ARR is above 43.45, PA may be considered and further confirmation is needed to prevent misdiagnosis.%目的:探讨最适于临床筛查原发性醛固酮增多症( PA)的方案。方法收集疑诊PA的病例303例,分为PA组、原发性高血压组和无功能性肾上腺皮质意外瘤组。利用血浆醛固酮/肾素浓度比值( ARR)绘制受试者工作特征( ROC)曲线,获取最佳诊断界值。进一步对目前临床关于PA筛查的方案进行对比分析。结果立位ARR的ROC曲线下面积明显高于卧位ARR及立、卧位血浆肾素、醛固酮。立位ARR诊断PA的最佳诊断界值[( pg/ml )/(μIU/ml)]为43.45,两次立、卧位试验中至少一次立位ARR >43.45时诊断PA的灵敏度最高,达0.94;两次立位ARR均<43.45时

  16. Correlation of reversely increased level of plasma glucose during pregnancy to the pregnancy outcome

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    Xiao-ya SHEN

    2017-02-01

    Full Text Available Objective To explore the correlation of the reversely increased results of 75g oral glucose tolerance test (OGTT during pregnancy to the pregnancy outcome, so as to provide a reliable theoretical basis of the early intervention for the pregnant women with high plasma glucose. Methods The clinical data of 461 cases were retrospectively analyzed. Patients were chosen from the pregnant women undergoing routine antenatal examination in our hospital during 2014. According to the results of 75g OGTT, 226 patients were analyzed as the observation group, in whom the level of postprandial 2-hour plasma glucose was higher than that of postprandial 1-hour plasma glucose. Meanwhile 235 pregnant women with or without gestational diabetes mellitus (GDM were randomly selected as the control group. Results The levels of fasting plasma glucose and 1-hour postprandial plasma glucose were lower, but those of 2-hour postprandial plasma glucose was higher in observation group than in control group (P0.05 in the incidences of polyhydramnios, oligohydramnios, fetal growth restriction (FGR, premature labor (PTL, pregnancy induced hypertension (PIH, complicated with premature rupture of membrane (PROM, intrauterine fetal death (IUFD and non scar uterus cesarean section rate (CSR. Compared with the observation group, the rates of neonatal dysplasia and neonatal asphyxia and the newborn transfer rate were lower in the control group, of which the newborn transfer rate was statistically different (P<0.01. Conclusions There might be a delayed plasma glucose metabolism in the patients with reversely increased result of 75g OGTT during pregnancy, which may affect the long-term prognosis of the newborn. Therefore, more attention should be paid to such patients with reversely increased result of 75g OGTT. DOI: 10.11855/j.issn.0577-7402.2017.01.09

  17. Increased plasma levels of Lp(a) enhance the development of coronary atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    LI Ying; XU Hong; ZHOU Qin; WANG Chang-yuan; LIU Yan-xia; LU Yuan-yuan; FAN Jiang-lin; SUN Hui-jun

    2008-01-01

    Objective To test the hypothesis that increased plasma levels of Lp(a) may enhance the development of atherosclerosis in the setting of hypercholesterolemia. Methods The plasma Lp(a) was analyzed by SDS-PAGE Western blotting and quantitated using specific ELISA kits. Plasma total cholesterol, triglycerides and HDL-cholesterol were determined using Wako assay kits. The left coronary artery was used for the evaluation of coronary atherosclerosis (stenosis %). For quantitative study of the lesions in coronary atherosclerosis, hematoxylin- eosin and Elastica - van Gieson staining were used. To study cellular components ( SMC vs. macrophages) and Lp(a) deposits in the lesions, immunohistochemical staining was performed and then image analysis system was used. Results Plasma total cholesterol, triglycerides, or HDL-C were not significantly different between transgenic (Trg) and nontransgenic (nonTrg) rabbits. Trg rabbits had 200 % increase in coronary stenosis caused by atherosclerosis. The lesions of Trg WHHL rabbits contained more SMCs and less macrophage than those of nonTrg WHHL rabbits. Conclusions The results suggest that increased plasma levels of Lp(a) enhance the development of coronary atherosclerosis.

  18. Habitual aerobic exercise increases plasma pentraxin 3 levels in middle-aged and elderly women.

    Science.gov (United States)

    Miyaki, Asako; Maeda, Seiji; Choi, Youngju; Akazawa, Nobuhiko; Tanabe, Yoko; Ajisaka, Ryuichi

    2012-10-01

    Chronic inflammation that occurs with aging is one of the risk factors for cardiovascular disease. Regular exercise may prevent cardiovascular morbidity by decreasing chronic systematic inflammation. Additionally, excess inflammation can be reduced by the anti-inflammatory protein pentraxin 3 (PTX3). Thus, both habitual exercise and PTX3 have an anti-inflammatory effect. However, it is unclear whether regular exercise leads to increased plasma PTX3 concentration. In the present study, we investigated the effects of regular aerobic exercise on plasma PTX3 concentration in middle-aged and elderly women. Twenty-two postmenopausal women (60 ± 6 years) were randomly divided evenly into 2 groups (i.e., exercise intervention and control). Subjects in the exercise group completed 2 months of regular aerobic exercise training (walking and cycling, 30-45 min, 3-5 days·week⁻¹). Before and after the intervention, we evaluated plasma PTX3 concentration, peak oxygen uptake, blood chemistry, and arterial distensibility (carotid arterial compliance and β-stiffness) in all participants. There were no significant differences in baseline parameters between the 2 groups. Plasma PTX3 concentration was significantly increased in the exercise group after the intervention (p exercise increases plasma PTX3 concentration with improvement of high-density lipoprotein cholesterol, peak oxygen uptake, and arterial distensibility in postmenopausal women.

  19. Increased Levels of Sphingosylphosphorylcholine (SPC in Plasma of Metabolic Syndrome Patients.

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    Nahed El-Najjar

    Full Text Available Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163. Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation.

  20. Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients.

    Science.gov (United States)

    El-Najjar, Nahed; Orsó, Evelyn; Wallner, Stefan; Liebisch, Gerhard; Schmitz, Gerd

    2015-01-01

    Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation.

  1. Plasma lactate concentration increases as a parabola with delay during ramp exercise.

    Science.gov (United States)

    Péronnet, F; Morton, R H

    1994-01-01

    This study presents an elementary model of a system which relates plasma lactate concentration ([La-]) during ramp exercise to its rate of accumulation (Rc) within its extramuscular distribution space (S). Under the parsimonious assumptions that Rc increases linearly with time (t) with a kinetic delay (delta), and that the volume of S is constant, it is shown that plasma [La-] increases as a parabola with the kinetic delay delta when t increases. This elementary system model describes changes in plasma [La-] observed in five healthy young subjects during ramp exercise on the cycle ergometer (1 W every 2 s) with great accuracy (r > 0.99) with very small residuals (average value less than 0.01 mmol.l-1), randomly distributed around the fitting curves. The delay between the beginning of exercise and the onset of increase in Rc could be due to the fact that at the corresponding work rates: (1) rate of lactate appearance (Ra), which is equal to the rate of lactate disappearance (Rd), is not modified from rest, since the exercising muscles work in fully aerobic conditions (hypothesis of the anaerobic threshold); or (2) the increase in Ra is associated with a similar increase in Rd. An alternate or complementary hypothesis is that, during ramp exercise, plasma [La-] could reflect metabolic events within the muscles, with a significant delay.

  2. Hypotonicity-induced Renin exocytosis from juxtaglomerular cells requires aquaporin-1 and cyclooxygenase-2

    DEFF Research Database (Denmark)

    Friis, Ulla G; Madsen, Kirsten; Svenningsen, Per

    2009-01-01

    The mechanism by which extracellular hypotonicity stimulates release of renin from juxtaglomerular (JG) cells is unknown. We hypothesized that osmotically induced renin release depends on water movement through aquaporin-1 (AQP1) water channels and subsequent prostanoid formation. We recorded...... membrane capacitance (C(m)) by whole-cell patch clamp in single JG cells as an index of exocytosis. Hypotonicity increased C(m) significantly and enhanced outward current. Indomethacin, PLA(2) inhibition, and an antagonist of prostaglandin transport impaired the C(m) and current responses to hypotonicity...

  3. Blood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

    Science.gov (United States)

    Wang, Peng; Li, Xin; Li, Xuran; Yang, Weiwei

    2016-01-01

    A pathological hallmark of Parkinson's disease (PD) is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-syn phosphorylation and oligomerization than plasma from normal subjects (NS). Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular α-syn. This was supported by the observations that phosphorylated α-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of α-syn aggregates via an alternative pathway and accelerate progression of PD. PMID:27965913

  4. Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

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    Peng Wang

    2016-01-01

    Full Text Available A pathological hallmark of Parkinson’s disease (PD is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of α-synuclein (α-syn aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-syn phosphorylation and oligomerization than plasma from normal subjects (NS. Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular α-syn. This was supported by the observations that phosphorylated α-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of α-syn aggregates via an alternative pathway and accelerate progression of PD.

  5. Expression of local renin and angiotensinogen mRNA in cirrhotic portal hypertensive patient

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Zhen Yang; Bao-Min Shi; Da-Peng Li; Chong-Yun Fang; Fa-Zu Qiu

    2003-01-01

    AIM: To investigate the expression of local renin and angiotensinogen mRNA in cirrhotic portal hypertensive patients.METHODS: The expression of local renin and angiotensinogen mRNA in the liver, splenic artery and vein of PH patients was detected by RT-PCR analysis.RESULTS: Expression of local renin mRNA in the liver of control group was (0.19±0.11), significantly lower than that in splenic artery(0.45±0.17)or splenic vein(0.39±0.12)respectively, (P<0.05). Expression of local angiotensinogen mRNA in the liver was (0.64±0.21), significantly higher than that in splenic artery(0.41±0.15) or in splenic vein (0.35±0.18)respectively, (P<0.05). Expression of local renin mRNA in the liver, splenic artery and vein of PH group was (0.78±0.28),(0.86±0.35) and (0.81±0.22) respectively, significantly higher than that in the control group, (P<0.05). Expression of local angiotensinogen mRNA in the liver, splenic artery and vein of PH group was (0.96±0.25), (0.83±0.18) and (0.79±0.23)respectively, significantly higher than that in the control group,(P<0.05). There was no significant difference between the liver, splenic artery and vein in the expression of local renin or local angiotensinogen mRNA in PH group, (P<0.05).CONCLUSION: In normal subjects the expression of local renin and angiotensinogen mRNA was organ specific, but with increase of the expression of LRAS, the organ-specificity became lost in cirrhotic patients. LRAS may contribute to increased resistance of portal vein with liver and formation of splanchnic vasculopathy.

  6. Increased plasma soluble CD40 ligand concentration in pelvic inflammatory disease.

    Science.gov (United States)

    Ho, Tsung-chin; Yang, Shun-Fa; Wang, Po-Hui; Lin, Long-Yau; Tee, Yi-Torng; Liao, Wen-Chun; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

    2015-01-01

    The role of soluble CD40 ligand (sCD40L) in pelvic inflammatory disease (PID) remains unclear. We sought to determine whether sCD40L was an efficient serum marker as with WBC and CRP in PID patients. Enzyme-linked immunosorbent assay was used to measure the plasma levels of sCD40L before and after routine protocol treatments in sixty-four PID patients and seventy healthy controls. The level of plasma sCD40L (pg/ml) was significantly elevated in PID patients (1632.83±270.91) compared to that in normal controls (700.33±58.77; p=0.001) and decreased significantly as compared to that in the same patients (928.77±177.25; p=0.0001) after they received treatment. The concentration of sCD40L was significantly correlated with the level of plasma C-reactive protein (CRP) in the blood (r=0.202, p=0.01, n=134). When the cutoff level of plasma sCD40L levels was determined to be 1612.26pg/ml based on ROC, the sensitivity, specificity, and the area under the curve of plasma sCD40L level for predicting PID were 0.26, 0.97, and 0.58 (95% confidence interval: 0.48-0.68), respectively, while the adjusted odds ratio (AOR) with their 95% CI of plasma sCD40L for PID risk was 7.09 (95% CI=1.14-43.87, p=0.03). The expression of plasma sCD40L was increased in patients with PID and detection of plasma sCD40L could be useful for the diagnosis of PID. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Supplementation of milled chia seeds increases plasma ALA and EPA in postmenopausal women.

    Science.gov (United States)

    Jin, Fuxia; Nieman, David C; Sha, Wei; Xie, Guoxiang; Qiu, Yunping; Jia, Wei

    2012-06-01

    Ten postmenopausal women (age 55.6 ± 0.8 years, BMI 24.6 ± 1.1 kg/m²) ingested 25 g/day milled chia seed during a 7-week period, with six plasma samples collected for measurement of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Subjects operated as their own controls with overnight fasted blood samples taken at baseline (average of two samples), and then after 1, 2, 3, 5, and 7 weeks supplementation. Plasma ALA increased significantly after one week supplementation and was 138 % above baseline levels by the end of the study (overall time effect, P chia seeds for seven weeks by postmenopausal women resulted in significant increases in plasma ALA and EPA but not DPA and DHA.

  8. Endothelin-1 concentration in plasma is increased after jogging but decreased after cycling in healthy men.

    Science.gov (United States)

    Lewczuk, P; Söhnchen, N; Kele, H; Reimers, C D; Ehrenreich, H

    2003-02-01

    Endothelin-1 plays an important role as a paracrine factor in the regulation of regional blood flow. Plasma levels may represent the net result of spill-over from local stimulation/release and elimination of endothelin-1. In order to compare changes in the concentration of endothelin-1 in the plasma of subjects performing different types of sports exercises we measured immunoreactive endothelin-1 in healthy volunteers ( n=20) performing in random order jogging on a treadmill and cycling on a bicycle ergometer, for 30 min each. Plasma immunoreactive endothelin-1 increased significantly after jogging (2.13+/-0.8 pg/ml versus 2.6+/-0.8 pg/ml, before and after exercise, respectively, Pjogging than during cycling, resulting in a greater increase in plasma endothelin-1, which is too high to be immediately eliminated by the lung despite exercise-induced enhanced pulmonary perfusion. In contrast, similarly enhanced lung perfusion together with a relatively lower stimulation of endothelin-1 compared with jogging, may explain the net decrease in plasma after cycling.

  9. Higher Plasma Pyridoxal Phosphate Is Associated with Increased Antioxidant Enzyme Activities in Critically Ill Surgical Patients

    Directory of Open Access Journals (Sweden)

    Chien-Hsiang Cheng

    2013-01-01

    Full Text Available Critically ill patients experience severe stress, inflammation and clinical conditions which may increase the utilization and metabolic turnover of vitamin B-6 and may further increase their oxidative stress and compromise their antioxidant capacity. This study was conducted to examine the relationship between vitamin B-6 status (plasma and erythrocyte PLP oxidative stress, and antioxidant capacities in critically ill surgical patients. Thirty-seven patients in surgical intensive care unit of Taichung Veterans General Hospital, Taiwan, were enrolled. The levels of plasma and erythrocyte PLP, serum malondialdehyde, total antioxidant capacity, and antioxidant enzyme activities (i.e., superoxide dismutase (SOD, glutathione S-transferase, and glutathione peroxidase were determined on the 1st and 7th days of admission. Plasma PLP was positively associated with the mean SOD activity level on day 1 (r=0.42, P<0.05, day 7 (r=0.37, P<0.05, and on changes (Δ (day 7 − day 1 (r=0.56, P<0.01 after adjusting for age, gender, and plasma C-reactive protein concentration. Higher plasma PLP could be an important contributing factor in the elevation of antioxidant enzyme activity in critically ill surgical patients.

  10. Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life.

    Science.gov (United States)

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-02-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  11. Renin inhibitor in hypertension treatment: from pharmacological point of view

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    Johannes Hudyono

    2011-08-01

    Full Text Available The use of drugs that inhibit the renin-angiotensin system is one of the effective way to intervene in the pathogenesis of cardiovascular and renal disorders, especially in hypertension treatment. The idea of blocking the renin system at its origin by renin inhibitor has existed for more than 30 years. Renin inhibitor supresses the covension of angiotensinogen into angiotensin, and further deacreases the generation of the active peptide angiotensin II. The first generation (enalkiren and second generation (remikiren of orally active renin inhibitors were never used clinically because of low bioavailability and weak blood pressure-lowering activity. At present, aliskiren is the first non-peptide orally active renin inhibitor of the third generation to progress to phase III clinical trials and was approved by U.S. Food and Drug Administration (FDA in March 2007. Aliskiren becomes the first renin inhibitor with indications for the treatment of hypertension in Indonesia, a compounds with improved oral bioavailability, specificity and efficacy. This review summarises the development of oral renin inhibitors, pharmacological aspects, with a focus on aliskiren. (Med J Indones 2011; 20:232-7Keywords: aliskiren, hypertension, renin inhibitor, renin-angiotensin

  12. Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren.

    Science.gov (United States)

    Stanton, Alice; Jensen, Chris; Nussberger, Juerg; O'Brien, Eoin

    2003-12-01

    Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal. Aliskiren, the first known representative of a new class of completely nonpeptide, orally active, renin inhibitors, has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure (BP) in sodium-depleted marmosets. The aim of this randomized, double-blind, active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension, were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or 100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime ambulatory systolic pressure (mean change, mm Hg [SD of change]; -0.4 [11.7], -5.3 [11.3], -8.0 [11.0], and -11.0 [11.0], P=0.0002) and in plasma renin activity (median change % [interquartile range]; -55 [-64, -11], -60 [-82, -46], -77 [-86, -72], and -83 [-92, -71], P=0.0008) were observed with 37.5, 75, 150, and 300 mg aliskiren. The change in daytime systolic pressure with 100 mg losartan (-10.9 [13.8]) was not significantly different from the changes seen with 75, 150, and 300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study demonstrates that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent. Whether renin inhibition results in protection from heart attack, stroke, and nephropathy, similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade, needs to be researched.

  13. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Vestbo, J

    2001-01-01

    We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD...

  14. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    OpenAIRE

    Schilling Brian K; Hammond Kelley G; Fisher-Wellman Kelsey H; Bloomer Richard J; Weber Adrianna A; Cole Bradford J

    2009-01-01

    Abstract Correction to Richard J Bloomer, Kelsey H Fisher-Wellman, Kelley G Hammond, Brian K Schilling, Adrianna A Weber and Bradford J Cole: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. Journal of the International Society of Sports Nutrition 2009, 6: 4

  15. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    Directory of Open Access Journals (Sweden)

    Schilling Brian K

    2009-04-01

    Full Text Available Abstract Correction to Richard J Bloomer, Kelsey H Fisher-Wellman, Kelley G Hammond, Brian K Schilling, Adrianna A Weber and Bradford J Cole: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. Journal of the International Society of Sports Nutrition 2009, 6: 4

  16. Acute elevation of plasma PLTP activity strongly increases pre-existing atherosclerosis

    NARCIS (Netherlands)

    M. Moerland (Matthijs); H.M.E. Samyn (Hannelore); T. van Gent (Teus); M.J. van Haperen (Rien); G.M. Dallinga-Thie (Geesje); F.G. Grosveld (Frank); A. van Tol (Arie); M.P.G. de Crom (Rini)

    2008-01-01

    textabstractObjective - A transgenic mouse model was generated that allows conditional expression of human PLTP, based on the tetracycline-responsive gene system, to study the effects of an acute increase in plasma PLTP activity as may occur in inflammation. Methods and Results - The effects of an a

  17. Fasting and prolonged exercise increase vasoactive intestinal polypeptide (VIP) in plasma

    DEFF Research Database (Denmark)

    Galbo, H; Hilsted, J; Fahrenkrug, J

    1979-01-01

    and maximal exercise. During 59 h of fasting, VIP increased from 3.6 (0.6--6.6) to 10.2 (6.6--13.8) pmol.1(-1) (p less than 0.05). The concentration of glucose in plasma decreased significantly during the prolonged exercise as well as during fasting. The known metabolic actions of VIP and the demonstrated...

  18. Fibrinogen γ' increases the sensitivity to activated protein C in normal and factor V Leiden plasma.

    Science.gov (United States)

    Omarova, Farida; Uitte de Willige, Shirley; Simioni, Paolo; Ariëns, Robert A S; Bertina, Rogier M; Rosing, Jan; Castoldi, Elisabetta

    2014-08-28

    Activated protein C (APC) resistance, often associated with the factor V (FV) Leiden mutation, is the most common risk factor for venous thrombosis. We observed increased APC resistance in carriers of fibrinogen γ gene (FGG) haplotype 2, which is associated with reduced levels of the alternatively spliced fibrinogen γ' chain. This finding prompted us to study the effects of fibrinogen and its γ' chain on APC resistance. Fibrinogen, and particularly the γA/γ' isoform, improved the response of plasma to added APC in the thrombin generation-based assay. Similarly, a synthetic peptide mimicking the C-terminus of the fibrinogen γ' chain, which binds thrombin and inhibits its activities, greatly increased the APC sensitivity of normal and FV Leiden plasma, likely due to its ability to inhibit thrombin-mediated activation of FV and FVIII. Although the fibrinogen γ' peptide also inhibited protein C activation by the thrombin/thrombomodulin complex, it still increased the sensitivity of plasma to endogenously formed APC when thrombin generation was measured in the presence of soluble thrombomodulin. We conclude that fibrinogen, and particularly fibrinogen γ', increases plasma APC sensitivity. The fibrinogen γ' peptide might form the basis for pharmacologic interventions to counteract APC resistance. © 2014 by The American Society of Hematology.

  19. Red wine prevents the postprandial increase in plasma cholesterol oxidation products: a pilot study.

    Science.gov (United States)

    Natella, F; Macone, A; Ramberti, A; Forte, M; Mattivi, F; Matarese, R M; Scaccini, C

    2011-06-28

    Moderate wine consumption has been shown to lower cardiovascular risk. One of the mechanisms could involve the control of postprandial hyperlipaemia, a well-defined risk factor for atherosclerosis, reasonably by reducing the absorption of lipid oxidised species from the meal. The objective of the present study was to investigate whether wine consumption with the meal is able to reduce the postprandial increase in plasma lipid hydroperoxides and cholesterol oxidation products, in human subjects. In two different study sessions, twelve healthy volunteers consumed the same test meal rich in oxidised and oxidisable lipids (a double cheeseburger), with 300 ml of water (control) or with 300 ml of red wine (wine). The postprandial plasma concentration of cholesterol oxidation products was measured by GC-MS. The control meal induced a significant increase in the plasma concentration of lipid hydroperoxides and of two cholesterol oxidation products, 7-β-hydroxycholesterol and 7-ketocholesterol. The postprandial increase in lipid hydroperoxides and cholesterol oxidation products was fully prevented by wine when consumed with the meal. In conclusion, the present study provides evidence that consumption of wine with the meal could prevent the postprandial increase in plasma cholesterol oxidation products.

  20. Alpha-lactalbumin combined with a regular diet increases plasma Trp-LNAA ratio

    NARCIS (Netherlands)

    Beulens, J.W.J.; Bindels, J.G.; Graaf, de C.

    2004-01-01

    Brain serotonin influences food intake and mood. It is synthesised from tryptophan (Tip) of which uptake in the brain is dependent on plasma ratio of tryptophan to the sum of other large neutral amino acids (Trp-LNAA). A carbohydrate-rich diet increases this ratio, whereas a protein-rich diet decrea

  1. Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as marker of SCAD defect and ethylmalonic encephalopathy

    DEFF Research Database (Denmark)

    Merinero, B; Perez-Cerda, C; Ruiz Sala, P

    2007-01-01

    High concentrations of butyryl/isobutyrylcarnitine (C(4)-carnitine) in plasma with increase of ethylmalonic acid (EMA) in urine point to different genetic entities, and further investigations are required to differentiate the possible underlying defect. Here we report three unrelated cases, two...

  2. Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology.

    Science.gov (United States)

    Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Desevaux, Cyril; Deurinck, Mark; Giraudel, Jérôme M; Danhof, Meindert

    2013-11-01

    The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age. Although observations of time-variant changes in the renin cascade are available in dogs, no detailed chronobiological investigation has been conducted so far. The present studies were designed to explore the circadian variations of plasma renin activity (RA) and urinary aldosterone-to-creatinine ratio (UA:C) in relation to blood pressure (BP), sodium (UNa, UNa,fe), and potassium (UK, UK,fe) renal handling. Data derived from intensive blood and urine sampling, as well as continuous BP monitoring, were collected throughout a 24-h time period, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of day and night observations were compared by parametric statistics. Our results show that variables of the renin cascade, BP, and urinary electrolytes oscillate with significant day-night differences in dogs. An approximately 2-fold (1.6-3.2-fold) change between the average day and night measurements was found for RA (p chronobiology of the renin cascade.

  3. Wire number doubling in plasma-shell regime increases z-accelerator x-ray power

    Energy Technology Data Exchange (ETDEWEB)

    Sanford, T.W.L.; Spielman, R.B.; Chandler, G.A. [and others

    1997-11-01

    Doubling the number of tungsten wires from 120 to 240, keeping the mass fixed, increased the radiated x-ray power relative to the electrical power at the insulator stack of the z accelerator by (40{+-}20)% for 8.75- and 20-mm-radii z-pinch wire arrays. Radiation-magneto-hydrodynamic calculations suggest that the arrays were operating in the {open_quotes}plasma shell{close_quotes} regime, where the plasmas generated by the individual wires merge prior to the inward implosion of the entire array.

  4. Dopamine plasma clearance is increased in piglets compared to neonates during continuous dopamine infusion

    DEFF Research Database (Denmark)

    Rasmussen, Martin B; Gramsbergen, Jan Bert; Eriksen, Vibeke R

    2017-01-01

    AIM: Piglets models have often been used to study the effects of dopamine infusion on hypotension in neonates. However, piglets need higher doses of dopamine than neonates to increase blood pressure. We investigated whether this difference was due to interspecific difference in dopamine...... pharmacokinetics. METHODS: Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.......5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection. RESULTS: The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma...

  5. Aortic Pathology and the Role of the Renin-Angiotensin System

    NARCIS (Netherlands)

    E. Moltzer (Els)

    2011-01-01

    textabstractThoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with beta-blockers. Increasing evidence supports a role for the renin-angiote

  6. Carbon dioxide-induced anesthesia results in a rapid increase in plasma levels of vasopressin.

    Science.gov (United States)

    Reed, Brian; Varon, Jack; Chait, Brian T; Kreek, Mary Jeanne

    2009-06-01

    Brief anesthesia, such as after exposure to high levels of carbon dioxide, prior to decapitation is considered a more humane alternative for the euthanasia of rodents, compared with use of decapitation alone. Studies of the levels of certain stress hormones in plasma such as corticosterone and ACTH have supported the use of this method of euthanasia in endocrinological and molecular studies. In the current study, rats were briefly exposed to a chamber filled with carbon dioxide until recumbent (20-25 sec), immediately killed via decapitation, and trunk blood collected; findings were compared with rats killed via decapitation with no exposure to carbon dioxide. RIAs were used to measure arginine vasopressin (AVP) and ACTH immunoreactivity (ir) in plasma. Whereas ACTH-ir levels remained steady after brief exposure to carbon dioxide (in accordance with results of other investigators), AVP-ir levels were increased by more than an order of magnitude. These results were confirmed by quantitative capillary-liquid chromatography-mass spectrometry, indicating this observation of rapid increase in plasma AVP-ir levels is not due to nonspecific recognition by the antibody used in the RIA. Likewise, using capillary-liquid chromatography-mass spectrometry, we observed a rapid increase in plasma oxytocin levels after carbon dioxide exposure. These surprising findings have important implications for the design and interpretation of studies involving brief carbon dioxide exposure prior to decapitation as well as those with euthanasia resulting from carbon dioxide-induced asphyxiation.

  7. Social instability increases plasma testosterone in a year-round territorial neotropical bird

    Science.gov (United States)

    Wikelski, M.; Hau, M.; Wingfield, J. C.

    1999-01-01

    In many vertebrates, elevated levels of plasma testosterone (T) are important for reproduction and territorial aggression. However, many tropical birds reproduce and defend territories while plasma T-levels are basal. We studied how aggression and T-levels are regulated in male neotropical spotted antbirds, which defend territories year-round in the Panamanian rainforest. Although spotted antbirds reproduce seasonally, T-levels of individual males often remained at baseline (0.2 ng ml-1) throughout the year, even in courting males. On the other hand, T-levels were elevated (maximally to 1.57 ng ml-1) during periods of social instability at any time of the year, even when males had entirely regressed gonads. Experimental territorial intrusions (broadcast of conspecific song) confirmed these observations by showing that T-levels increased after about two hours of playback time. Our data suggest that spotted antbirds avoided the potential costs associated with constantly high plasma T-levels (e.g. increased mortality rates). Contrary to temperate zone birds, spotted antbirds had the potential to react to social challenges with an increase of plasma T year-round. These results are, to our knowledge, presently unique, but may apply to many vertebrate species that inhabit the tropics.

  8. Plasma bactericidal/permeability-increasing protein concentrations in critically ill children with the sepsis syndrome.

    Science.gov (United States)

    Wong, H R; Doughty, L A; Wedel, N; White, M; Nelson, B J; Havrilla, N; Carcillo, J A

    1995-12-01

    Bactericidal/permeability-increasing protein (BPI) is a neutrophil azurophilic granule component that is bactericidal towards Gram-negative bacteria and inhibits lipopolysaccharide-mediated inflammatory responses. We conducted a prospective study to measure plasma BPI concentrations in 36 critically ill children with and without the sepsis syndrome. Plasma BPI concentrations ranged from 0.5 to 452 ng/ml. Patients with the sepsis syndrome had higher median plasma BPI concentrations than critically ill controls (5.1 vs. 1.8 ng/ml, P = 0.006). Patients with organ system failure had higher median plasma BPI concentrations than those with no organ system failure (4.5 vs. 1.3 ng/ml, P = 0.001). Plasma BPI concentrations were positively associated with pediatric risk of mortality score (P = 0.03, rs = 0.4). These data provide the first clinical insights regarding the role of endogenous BPI production in critically ill children and suggest that BPI may play an important role in host defenses.

  9. Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women.

    Science.gov (United States)

    Matsubara, Tomoko; Miyaki, Asako; Akazawa, Nobuhiko; Choi, Youngju; Ra, Song-Gyu; Tanahashi, Koichiro; Kumagai, Hiroshi; Oikawa, Satoshi; Maeda, Seiji

    2014-02-01

    The Klotho gene is a suppressor of the aging phenomena, and the secretion as well as the circulation of Klotho proteins decrease with aging. Although habitual exercise has antiaging effects (e.g., a decrease in arterial stiffness), the relationship between Klotho and habitual exercise remains unclear. In the present study, we investigated the effect of habitual exercise on Klotho, with a particular focus on arterial stiffness. First, we examined the correlation between plasma Klotho concentration and arterial stiffness (carotid artery compliance and β-stiffness index) or aerobic exercise capacity [oxygen uptake at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50-76 years old) by conducting a cross-sectional study. Second, we tested the effects of aerobic exercise training on plasma Klotho concentrations and arterial stiffness. A total of 19 healthy, postmenopausal women (50-76 years old) were divided into two groups: control group and exercise group. The exercise group completed 12 wk of moderate aerobic exercise training. In the cross-sectional study, plasma Klotho concentrations positively correlated with carotid artery compliance and VT and negatively correlated with the β-stiffness index. In the interventional study, aerobic exercise training increased plasma Klotho concentrations and carotid artery compliance and decreased the β-stiffness index. Moreover, the changes in plasma Klotho concentration and arterial stiffness were found to be correlated. These results suggest a possible role for secreted Klotho in the exercise-induced modulation of arterial stiffness.

  10. Increasing lifetime of the plasma channel formed in air using picosecond and nanosecond laser pulses

    Science.gov (United States)

    Narayanan, V.; Singh, V.; Pandey, Pramod K.; Shukla, Neeraj; Thareja, R. K.

    2007-04-01

    We report experiments on a pump-probe configuration to elucidate the formation of a plasma channel by the hydrodynamic evolution of air breakdown in laser focus. A stable air breakdown was produced by focusing a picosecond laser pulse to create a shock driven plasma channel in the laser focus for propagating a nanosecond pulse. A four fold increase in the lifetime of the channel estimated by monitoring the temporal evolution of the fluorescence of a spectral line at 504.5nm of N+ transition 3pS3-3sP03 is reported. Assuming plasma in local thermal equilibrium plasma temperature of ˜8.2eV and an electron density of ˜1.4×1018cm-3 were determined using a Stark broadening of 649.2nm line of NII transition 3dD03-4pD3 in the channel. An enhancement in the electron density of the plasma channel was observed at the 7ns delay of the nanosecond laser pulse relative to the picosecond laser pulse.

  11. The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects

    NARCIS (Netherlands)

    Roos, de B.; Caslake, M.J.; Stalenhoef, A.F.H.; Bedford, D.; Demacker, P.N.; Katan, M.B.; Packard, C.J.

    2001-01-01

    Background: Cafestol is a diterpene in unfiltered coffee that raises plasma triacylglycerol in humans. Objective: We studied whether cafestol increases plasma triacylglycerol by increasing the production rate or by decreasing the fractional catabolic rate of VLDL1 [Svedberg flotation unit (Sf) 60-40

  12. Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders.

    Directory of Open Access Journals (Sweden)

    Jaw-Shiun Tsai

    Full Text Available OBJECTIVE: Frailty is an important geriatric syndrome. Adiponectin is an important adipokine that regulates energy homeostasis. The aim of this study is to investigate the relationship between plasma adiponectin levels and frailty in elders. METHODS: The demographic data, body weight, metabolic and inflammatory parameters, including plasma glucose, total cholesterol, triglyceride, tumor necrosis factor alpha (TNF-α, c-reactive protein (CRP and adiponectin levels, were assessed. The frailty score was assessed using the Fried Frailty Index (FFI. RESULTS: The mean (SD age of the 168 participants [83 (49.4% men and 85 (50.6% women] was 76.86 (6.10 years. Judged by the FFI score, 42 (25% elders were robust, 92 (54.7% were pre-frail, and 34 (20.3% were frail. The mean body mass index was 25.19 (3.42 kg/m(2. The log-transformed mean (SD plasma adiponectin (µg/mL level was 1.00 (0.26. The log-transformed mean plasma adiponectin (µg/mL levels were 0.93 (0.23 in the robust elders, 1.00 (0.27 in the pre-frail elders, and 1.10 (0.22 in the frail elders, and the differences between these values were statistically significant (p  = 0.012. Further analysis showed that plasma adiponectin levels rose progressively with an increasing number of components of frailty in all participants as a whole (p for trend  = 0.024 and males (p for trend  = 0.037, but not in females (p for trend  = 0.223. CONCLUSION: Plasma adiponectin levels correlate positively with an increasing number of components of frailty in male elders. The difference between the sexes suggests that certain sex-specific mechanisms may exist to affect the association between adiponectin levels and frailty.

  13. Blockade of the renin-angiotensin system

    OpenAIRE

    Cheung, BMY.

    2002-01-01

    The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin-converting enzyme inhibitors inhibit angiotensin-converting enzyme and have been shown to be effective in many cardiovascular diseases. They should be considered for the treatment of hypertension in patients with heart failure, previous myocardial infarction, diabetes, or proteinuria. There are a number of side-effects associated with angiotensin-converting enzyme inhibito...

  14. Molecular biology of the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Dzau, V.J.; Burt, D.W.; Pratt, R.E. (Harvard Medical School, Boston, MA (USA))

    1988-10-01

    This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.

  15. Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis.

    Science.gov (United States)

    Rengarajan, Srinivas; Lee, Donna H; Oh, Young Taek; Delpire, Eric; Youn, Jang H; McDonough, Alicia A

    2014-05-01

    Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na(+)-Cl(-) cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na(+) reabsorption and shifts Na(+) downstream for reabsorption by epithelial Na(+) channels (ENaC), which can drive K(+) secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K(+) concentration ([K(+)]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K(+)] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K(+)] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K(+), Na(+), and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na(+)-K(+)-2Cl(-) cotransporter (NKCC) phosphorylation 25% (P = 0.055). When plasma [K(+)] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% (P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na(+)/H(+) exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K(+) channel. In summary, raising plasma [K(+)] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K(+) ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na(+) reabsorption and flow drive K(+) secretion.

  16. Increased plasma dopamine in patients presenting with the pseudopheochromocytoma quandary: retrospective analysis of 10 years' experience.

    Science.gov (United States)

    Kuchel, O

    1998-10-01

    A retrospective analysis was made to determine alternative diagnoses in patients with predominantly hypertensive episodes who were suspected of having pheochromocytoma but in whom this diagnosis was eliminated. Analysis of a random university hospital population referred over a period of 10 years. Episodic clinical presentations of pheochromocytoma symptoms combined with a comparison of baseline and episodic radioenzymatically determined levels of plasma free norepinephrine and epinephrine were examined, together with prospective levels of plasma free and sulfated dopamine. Out of 63 patients presenting with episodes of palpitations, headaches, flushing, sweating and hyperventilation (associated with hypertension in 49 patients, with hypotension in six patients and with alternating hyper- and hypotension in eight patients), 14 were diagnosed as having idiopathic hypovolemia, nine as having mastocytosis, nine as having an adrenal tumor, four as having neurogenic hypertension and one each with cocaine abuse and reninoma. Both baseline and symptomatic levels of plasma free norepinephrine and epinephrine remained within physiological limits (exceeding them moderately in baroreceptor dysfunction only), but all subgroups had a mean episodic increase over baseline in plasma dopamine sulfate (mean+/-SEM 16.7+/-5.9 to 53.2+/-19 pmol/ml; P pheochromocytoma in hemodynamic instability and frequent flushing formed a heterogeneous group, with plasma norepinephrine and epinephrine usually within physiological limits but an overall mean threefold increase in dopamine sulfate concentrations. With the various diagnoses of idiopathic hypovolemia, mastocytosis, neurogenic, secondary hypertension and cocaine abuse eliminated as a cause of pheochromocytoma-like symptoms, at least half of these patients still had unexplained, predominantly emotionally or proprioreceptive stimulation-provoked, bouts of hypertension. Sympathetic arousal dominated by an increase in dopamine sulfate without

  17. Increased plasma ghrelin suppresses insulin release in wethers fed with a high-protein diet.

    Science.gov (United States)

    Takahashi, T; Sato, K; Kato, S; Yonezawa, T; Kobayashi, Y; Ohtani, Y; Ohwada, S; Aso, H; Yamaguchi, T; Roh, S G; Katoh, K

    2014-06-01

    Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein (HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet.

  18. Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase.

    Science.gov (United States)

    Nakajima, Katsuyuki; Tokita, Yoshiharu; Sakamaki, Koji; Shimomura, Younosuke; Kobayashi, Junji; Kamachi, Keiko; Tanaka, Akira; Stanhope, Kimber L; Havel, Peter J; Wang, Tao; Machida, Tetsuo; Murakami, Masami

    2017-02-01

    Previous large population studies reported that non-fasting plasma triglyceride (TG) reflect a higher risk for cardiovascular disease than TG in the fasting plasma. This is suggestive of the presence of higher concentration of remnant lipoproteins (RLP) in postprandial plasma. TG and RLP-TG together with other lipids, lipoproteins and lipoprotein lipase (LPL) in both fasting and postprandial plasma were determined in generally healthy volunteers and in patients with coronary artery disease (CAD) after consuming a fat load or a more typical moderate meal. RLP-TG/TG ratio (concentration) and RLP-TG/RLP-C ratio (particle size) were significantly increased in the postprandial plasma of both healthy controls and CAD patients compared with those in fasting plasma. LPL/RLP-TG ratio demonstrated the interaction correlation between RLP concentration and LPL activity The increased RLP-TG after fat consumption contributed to approximately 90% of the increased plasma TG, while approximately 60% after a typical meal. Plasma LPL in postprandial plasma was not significantly altered after either type of meal. Concentrations of RLP-TG found in the TG along with its particle size are significantly increased in postprandial plasma compared with fasting plasma. Therefore, non-fasting TG determination better reflects the presence of higher RLP concentrations in plasma. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Chronic effects of lead on renin and renal sodium excretion. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, N.; Mouw, D.R.; Vander, A.J.

    1980-05-01

    Rats were chronically give 0.5 mg/ml Pb in drinking water. This produced blood and renal lead concentratoins of approximately 30 )g/dl and 20)g/gm, respectively, significant kidney swelling, but no change in body weight or hematocrit. After 6 weeks of Pb treatment and during ingestion of a sodium-free diet, plasma, renin activity (PRA) was elevated (controls: same diet, no lead), but there was no change in plasma resin substrate (PRS). After 5 months the PRA was significantly higher in the lead-treated group even on a 1% NaCl diet, but the difference between groups disappeared on an Na-free diet; that is, the renin response to sodium deprivation was blunted. As early as 6 weeks after beginning lead treatment, the treated group manifested reduced ability to decrease Na excretion following removal of NaCl from the diet; steady-state sodium excretion was normal on either the 1% NaCl or Na-free diet. We conclude that changes in the renin angiotensin system and renal sodium handling may be important toxic effects of low doses of lead on the kidneys of rats.

  20. Fundamental and clinical study of direct immunoradiometric assay in human renin concentration

    Energy Technology Data Exchange (ETDEWEB)

    Kurimoto, Fumihiko; Horiuchi, Junko; Sakurai, Hyoichiro; Suzuki, Hiromichi; Takita, Takashi; Saruta, Takao.

    1988-05-01

    'Renin RIA Pasteur' kit for directly measuring renin concentration in human plasma (PRC) was fundamentally and clinically evaluated. A standard curve for PRC was linear in the range of 10 - 640 pg/ml. Reproducibility, recovery, and stability were satisfactory. There was a significantly positive correlation between direct PRC and conventional plasma renin activity (PRA) and indirect PRC. PRC was directly measured in 119 healthy volunteers and 15 patients with primary aldosteronism (4), Cushing's syndrome (6), or non-functioning tumor (5). The basal PRC was 32.4 +- 18.8 pg/ml for men and 37.9 +- 22.6 pg/ml for women. PRC for primary aldosteronism was below detectable levels, and remained unchanged even after the administratin of ACTH. In the case of Cushing's syndrome, mean PRC and PRA were 19 pg/ml and 1.2 ng/ml/hr, and did not respond to ACTH. Although the administration of ATCH was significantly associated with a decreased PRC, there was only tendency toward the decreased PRA in the case of non-functioning tumors. The results indicate the usefulness of the present kit in terms of its ability to directly measure PRC without any complicated procedures. (Namekawa, K.).

  1. Macula Densa Sensing and Signaling Mechanisms of Renin Release

    OpenAIRE

    Peti-Peterdi, János; Raymond C Harris

    2010-01-01

    Macula densa cells in the distal nephron, according to the classic paradigm, are salt sensors that generate paracrine chemical signals in the juxtaglomerular apparatus to control vital kidney functions, including renal blood flow, glomerular filtration, and renin release. Renin is the rate-limiting step in the activation of the renin-angiotensin system, a key modulator of body fluid homeostasis. Here, we discuss recent advances in understanding macula densa sensing and suggest these cells, in...

  2. Renin and angiotensinogen gene expression in maturing rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, R.A.; Lynch, K.R.; Chevalier, R.L.; Wilfong, N.; Everett, A.; Carey, R.M.; Peach, M.J. (Univ. of Virginia, Charlottesville (USA))

    1988-04-01

    To determine whether angiotensinogen (A{sub o}) and renin are synthesized by the immature kidney and to assess the changes in intrarenal reinin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and A{sub o} relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and A{sub o} cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I{center dot}h{sup {minus}1}{center dot}mg protein{sup {minus}1} in the incubation media. RRC was higher in newborn than in adult SHR (979 {+-} 164 vs. 206 {+-} 47) and WKY. In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animals. A{sub o} mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and A{sub o} genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.

  3. 不同体位血浆醛固酮浓度与肾素活性比及其联合血浆醛固酮浓度对醛固酮瘤的诊断价值%An evaluation of plasma aldosterone-to-active-renin ratio in different postures in combination with aldosterone concentration in the diagnosis of aldosteronoma

    Institute of Scientific and Technical Information of China (English)

    朱杰; 金楠; 臧丽; 谷伟军; 杨国庆; 杨丽娟; 郭清华; 王先令; 吕朝晖

    2016-01-01

    Objective To investigate the diagnostic value of plasma aldosterone-to-active-renin ratio (ARR) in combination with plasma aldosterone concentration(PAC)in the predication of aldosteronoma (APA).Methods A total of 85 APA and 155 essential hypertension(EH)patients from January 2012 to December 2014 in Chinese PLA General Hospital were enrolled.The ROC curve was applied to calculate the optimal cut-off points of ARR for APA.Results (1) The optimal cut-off point of supine ARR was 1707.4(pmol/L)/(μg· L-1 · h 1)[61.64(ng/dl)/(μg · L-1 · h-1)] with the sensitivity,specificity and accuracy of 89.41%,80.65% and 83.75%,respectively.The specificity and accuracy of the diagnostic value for APA increased (89.03% and 87.5% respectively) when supine ARR cut-off point were used in combination with supine PAC over 329.4 pmol/L.(2) The optimal cut-off point of upright ARR was 741.5 (pmol/L)/(μg · L-1 · h-1) [26.77 (ng/dl)/(μg · L-1 · h 1)] with the sensitivity,specificity and accuracy of 85.88%,91.61% and 89.58%,respectively.Similarly,the specificity and accuracy greatly improved (94.84% and 91.67%,respectively) when upright ARR were applied together with upright PAC over 323.1 pmol/L.Conclusions Both spine and upright ARR can be used in screening for APA.Moreover,the specificity and accuracy could be improved when ARR and PAC were used together both in the supine and upright position.%目的 探讨不同体位血浆醛固酮浓度(PAC)与肾素活性(PRA)之比(ARR)及其联合PAC对醛固酮瘤的诊断价值.方法 回顾性分析2012年1月-2014年12月解放军总医院确诊的85例醛固酮瘤及155例原发性高血压患者的临床资料,并计算ARR值,应用ROC曲线得出ARR的最佳切点.结果 (1)卧位ARR的最佳切点为1707.4(pmol/L)/(μg·L-1·h-1)[61.64(ng/dl)/(μg·L-1·h-1)],敏感度为89.41%,特异度为80.65%,准确性为83.75%;卧位ARR>1707.4(pmol/L)/(μg·L-1·h-1)[61.64(ng/dl)/(μg·L-1·h-1)]

  4. Macula densa sensing and signaling mechanisms of renin release.

    Science.gov (United States)

    Peti-Peterdi, János; Harris, Raymond C

    2010-07-01

    Macula densa cells in the distal nephron, according to the classic paradigm, are salt sensors that generate paracrine chemical signals in the juxtaglomerular apparatus to control vital kidney functions, including renal blood flow, glomerular filtration, and renin release. Renin is the rate-limiting step in the activation of the renin-angiotensin system, a key modulator of body fluid homeostasis. Here, we discuss recent advances in understanding macula densa sensing and suggest these cells, in addition to salt, also sense various chemical and metabolic signals in the tubular environment that directly trigger renin release.

  5. Increased fasting plasma acylation-stimulating protein concentrations in nephrotic syndrome.

    Science.gov (United States)

    Ozata, Metin; Oktenli, Cagatay; Gulec, Mustafa; Ozgurtas, Taner; Bulucu, Fatih; Caglar, Kayser; Bingol, Necati; Vural, Abdulgaffar; Ozdemir, I Caglayan

    2002-02-01

    Acylation-stimulating protein (ASP) is an adipocyte-derived protein that has recently been suggested to play an important role in the regulation of lipoprotein metabolism and triglyceride (TG) storage. ASP also appears to have a role in the regulation of energy balance. In addition to its role as a hormonal regulator of body weight and energy expenditure, leptin is now implicated as a regulatory molecule in lipid metabolism. However, little is known about the alterations in fasting plasma ASP and leptin concentrations in the nephrotic syndrome. As hyperlipidemia is one of the most striking manifestations of the nephrotic syndrome, we have investigated fasting plasma ASP and leptin levels and their relation to lipid levels in this syndrome. Twenty-five patients with untreated nephrotic syndrome and 25 age-, sex-, and body mass index-matched healthy controls were included in the study. Fasting plasma lipoproteins, TG, total cholesterol, lipoprotein(a), apolipoprotein AI (apoAI), apoB, urinary protein, plasma albumin, third component of complement (C3), ASP, and leptin levels were measured in both groups. Total cholesterol, TG, low and very low density lipoproteins, lipoprotein(a), apoB, and urinary protein levels were increased in the patient group, whereas plasma albumin, high density lipoprotein cholesterol, and apoAI levels were decreased compared with those in the control group (P Fasting ASP concentrations showed no correlation with body mass index, proteinuria, plasma albumin, leptin, or any lipid parameter in either group, but C3 levels (in patient group: r(s) = 0.92; P < 0.001; in control group: r(s) = 0.68; P < 0.001). Our findings showed that plasma ASP levels were significantly elevated, whereas leptin levels were normal in the nephrotic syndrome. Increased ASP levels in the setting of dyslipidemia in the nephrotic syndrome raise the possibility of an ASP receptor defect in adipocytes, which also suggests the existence of so-called ASP resistance. Moreover

  6. Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration.

    Science.gov (United States)

    Killilea, David W; Rohner, Fabian; Ghosh, Shibani; Otoo, Gloria E; Smith, Lauren; Siekmann, Jonathan H; King, Janet C

    2017-06-01

    Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations.Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC.Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry.Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale.Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions.

  7. Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration123

    Science.gov (United States)

    Otoo, Gloria E; Smith, Lauren; Siekmann, Jonathan H

    2017-01-01

    Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations. Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC. Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry. Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1–2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale. Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions. PMID

  8. Plasma insulin levels are increased by sertraline in rats under oral glucose overload

    Directory of Open Access Journals (Sweden)

    Gomez R.

    2001-01-01

    Full Text Available Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10. Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 ± 3.86, sertraline + fasting group: 31.10 ± 2.48, overload group: 34.1 ± 3.40, and overload + sertraline group: 43.73 ± 5.14 µU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

  9. Acute Exercise Increases Plasma Total Antioxidant Status and Antioxidant Enzyme Activities in Untrained Men

    Directory of Open Access Journals (Sweden)

    C. Berzosa

    2011-01-01

    Full Text Available Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects (=34 performed three cycloergometric tests, including maximal and submaximal episodes. Venous blood samples were collected before and immediately after each different exercise. TAS and enzyme activities were assessed by spectrophotometry. An increase of the antioxidant enzyme activities in plasma was detected after both maximal and submaximal exercise periods. Moreover, under our experimental conditions, exercise also led to an augmentation of TAS levels. These findings are consistent with the idea that acute exercise may play a beneficial role because of its ability to increase antioxidant defense mechanisms through a redox sensitive pathway.

  10. Continuous reduction of plasma paraoxonase activity with increasing dialysis vintage in hemodialysis patients.

    Science.gov (United States)

    Henning, Bernhard F; Holzhausen, Helge; Tepel, Martin

    2010-12-01

    Plasma paraoxonase (PON) is an enzyme that hydrolyzes organic phosphate and aromatic carboxylic acid esters. Reduced activity is associated with early events of atherogenesis. The relevance of PON phenotypes is not well characterized in hemodialysis patients. In a cross-sectional study we measured PON activity in 377 hemodialysis patients photometrically using the substrates 4-nitrophenylacetate and phenylacetate. The PON ratio was calculated from 4-nitrophenylacetate-derived activity divided by phenylacetate-derived activity. Frequency distribution of the PON ratio showed three different PON phenotypes. 74% of hemodialysis patients showed PON phenotype 1, 21% PON phenotype 2, and 5% PON phenotype 3. Compared to hemodialysis patients with PON 1, patients with PON 2 or 3 showed higher conversion rates for 4-nitrophenylacetate. We observed a significant reduction of PON ratio with increasing dialysis vintage (Pvintage. In conclusion, plasma PON ratio significantly declines with increasing dialysis vintage.

  11. Elevated plasma homocysteine is associated with increased brain atrophy rates in older subjects with mild hypertension.

    Science.gov (United States)

    Narayan, Sunil K; Firbank, Michael J; Saxby, Brian K; Stansby, Gerard; Hansrani, Monica; O'Brien, John T; Ford, Gary A

    2011-01-01

    We determined using serial MR imaging whether raised plasma homocysteine levels are associated with increased brain atrophy, white matter lesion (WML) progression or incidence of silent brain infarcts (SBIs) in older hypertensive subjects. Brain atrophy rates (0.58 ± 0.48% per year, mean ± SD) were significantly correlated with homocysteine (β = 0.46, p = 0.001 homocysteine; β = 0.44, p = 0.007 homocysteine/folate/B12 models) but not with folate or B12 levels. Progression of WML (0.08 ± 0.16%) was not associated with homocysteine level (B = 0.01, p = 0.29). New SBIs were uncommon. In older hypertensive individuals, plasma homocysteine levels are associated with increased rates of whole-brain atrophy but not WML progression.

  12. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure.

    Science.gov (United States)

    Patel, Vaibhav B; Zhong, Jiu-Chang; Grant, Maria B; Oudit, Gavin Y

    2016-04-15

    Heart failure (HF) remains the most common cause of death and disability, and a major economic burden, in industrialized nations. Physiological, pharmacological, and clinical studies have demonstrated that activation of the renin-angiotensin system is a key mediator of HF progression. Angiotensin-converting enzyme 2 (ACE2), a homolog of ACE, is a monocarboxypeptidase that converts angiotensin II into angiotensin 1-7 (Ang 1-7) which, by virtue of its actions on the Mas receptor, opposes the molecular and cellular effects of angiotensin II. ACE2 is widely expressed in cardiomyocytes, cardiofibroblasts, and coronary endothelial cells. Recent preclinical translational studies confirmed a critical counter-regulatory role of ACE2/Ang 1-7 axis on the activated renin-angiotensin system that results in HF with preserved ejection fraction. Although loss of ACE2 enhances susceptibility to HF, increasing ACE2 level prevents and reverses the HF phenotype. ACE2 and Ang 1-7 have emerged as a key protective pathway against HF with reduced and preserved ejection fraction. Recombinant human ACE2 has been tested in phase I and II clinical trials without adverse effects while lowering and increasing plasma angiotensin II and Ang 1-7 levels, respectively. This review discusses the transcriptional and post-transcriptional regulation of ACE2 and the role of the ACE2/Ang 1-7 axis in cardiac physiology and in the pathophysiology of HF. The pharmacological and therapeutic potential of enhancing ACE2/Ang 1-7 action as a novel therapy for HF is highlighted.

  13. Green tea supplementation increases glutathione and plasma antioxidant capacity in adults with the metabolic syndrome.

    Science.gov (United States)

    Basu, Arpita; Betts, Nancy M; Mulugeta, Afework; Tong, Capella; Newman, Emily; Lyons, Timothy J

    2013-03-01

    Green tea, a popular polyphenol-containing beverage, has been shown to alleviate clinical features of the metabolic syndrome. However, its effects in endogenous antioxidant biomarkers are not clearly understood. Thus, we tested the hypothesis that green tea supplementation will upregulate antioxidant parameters (enzymatic and nonenzymatic) in adults with the metabolic syndrome. Thirty-five obese participants with the metabolic syndrome were randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day). Blood samples and dietary information were collected at baseline (0 week) and 8 weeks of the study. Circulating carotenoids (α-carotene, β-carotene, lycopene) and tocopherols (α-tocopherol, γ-tocopherol) and trace elements were measured using high-performance liquid chromatography and inductively coupled plasma mass spectroscopy, respectively. Serum antioxidant enzymes (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity were measured spectrophotometrically. Green tea beverage and green tea extract significantly increased plasma antioxidant capacity (1.5 to 2.3 μmol/L and 1.2 to 2.5 μmol/L, respectively; P glutathione (1783 to 2395 μg/g hemoglobin and 1905 to 2751 μg/g hemoglobin, respectively; P glutathione peroxidase and catalase activities. Green tea extract significantly reduced plasma iron vs baseline (128 to 92 μg/dL, P green tea may provide antioxidant protection in the metabolic syndrome.

  14. Increased Plasma Dipeptidyl Peptidase-4 Activities in Patients with Coronary Artery Disease

    Science.gov (United States)

    Yang, Guang; Li, Yuzi; Cui, Lan; Jiang, Haiying; Li, Xiang; Jin, Chunzi; Jin, Dehao; Zhao, Guangxian; Jin, Jiyong; Sun, Rui; Piao, Limei; Xu, Wenhu; Fang, Chenghu; Lei, Yanna; Yuan, Kuichang; Xuan, Chunhua; Ding, Dazi

    2016-01-01

    Dipeptidyl peptidase-4 (DPP4) is one of the most potent mammalian serine proteases participated in the pathogenesis of subclinical atherosclerosis. Here we investigated whether the plasma soluble form of DPP4 is associated with the prevalence of coronary artery disease (CAD) with and without diabetes mellitus (DM). A cross-sectional study was conducted of 496 aged 26–81 years with (n = 362) and without (n = 134) CAD. Plasma DPP4 activity, high sensitive C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein levels were measured. The coronary atherosclerotic plaques were evaluated by coronary angiography. The CAD patients with (n = 84) and without (n = 278) DM had significantly higher DPP4 levels (11.8 ± 3.1 vs. 6.9 ± 3.5 ng/mL, Psyntax scores. A multiple logistic regression analysis demonstrated that plasma DPP4 activity was independent predictor of CAD (odds ratio, 1.56; 95% CI, 1.19–1.73; P<0.01). Our study shows that increased DPP4 activity levels are associated with the presence of CAD and that the plasma DPP4 level serves as a novel biomarker for CAD even without DM. PMID:27654253

  15. Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes.

    Science.gov (United States)

    Keser, Toma; Gornik, Ivan; Vučković, Frano; Selak, Najda; Pavić, Tamara; Lukić, Edita; Gudelj, Ivan; Gašparović, Hrvoje; Biočina, Bojan; Tilin, Therese; Wennerström, Annika; Männistö, Satu; Salomaa, Veikko; Havulinna, Aki; Wang, Wei; Wilson, James F; Charutvedi, Nishi; Perola, Markus; Campbell, Harry; Lauc, Gordan; Gornik, Olga

    2017-09-13

    Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes. Using a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA1c > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA1c > 6.5% [47.5 mmol/mol] vs 307 controls). Individuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA1c (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude. Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention

  16. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    OpenAIRE

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine

    2016-01-01

    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed to test this hypothesis by assessing bile acid and calcium concentrations in fecal samples from humans after intake of cheese and butter. Methods The study was a randomized, 2 × 6 weeks crossover, die...

  17. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    Science.gov (United States)

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability.

  18. The increase of plasma galectin-9 in a patient with insulin allergy: a case report

    Directory of Open Access Journals (Sweden)

    Chagan-Yasutan Haorile

    2010-08-01

    Full Text Available Abstract Allergic reaction to insulin is known to be associated with eosinophilia and hyper IgE. Recent report showed that eosinophilia is related with the increased synthesis of galectin-9 (GAL-9 and osteopontin (OPN. Here, we examined plasma levels of GAL-9 and OPN first time in a case of 65-year old patient with insulin allergy. Insulin aspart & insulin aspart 30 mix were given to the patient and an elevation of the eosinophil count (8440/μl, 17.6 fold and a moderate increase of IgE (501 U/ml, reference range: 10-350 U/ml, eotaxin-3 (168 pg/ml, 2 fold, histamine (0.95 ng/ml, 5.3 fold were found 33 days later. The plasma levels of GAL-9 and OPN were 22.5 and 1.7 fold higher than the cut-off point, respectively. After one month cessation of insulin therapy, elevations of the eosinophil count (3,480/μl; 7.3 fold, and OPN (1.4 fold still occurred but the GAL-9 levels became normal. Therefore, we noted the increases of GAL-9 and OPN in plasma for the first time in a patient with insulin allergy and propose that GAL-9 reflects the conditions of allergy more accurately.

  19. The role of the renin-angiotensin-aldosterone system in heart failure

    Directory of Open Access Journals (Sweden)

    Thomas Unger

    2004-03-01

    Full Text Available Activity of the renin-angiotensin-aldosterone system (RAAS is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third-generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease. Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II (in addition to angiotensin-converting enzyme [ACE], has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo. Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.

  20. Pressure-natriuresis and -diuresis in transgenic rats harboring both human renin and human angiotensinogen genes.

    Science.gov (United States)

    Dehmel, B; Mervaala, E; Lippoldt, A; Gross, V; Bohlender, J; Ganten, D; Luft, F C

    1998-12-01

    The hypertensive double transgenic rat harboring both the human renin and human angiotensinogen genes (dTGR) offers a unique opportunity to study the human renin-angiotensin system in an experimental animal model. Since nothing is known about the control of sodium and water excretion in these rats, this study was performed to compare pressure-natriuresis relationships in hypertensive dTGR and normotensive control rats harboring only the human renin gene (hREN), in order to determine how the pressure-natriuresis relationship is reset in hypertensive dTGR. To differentiate between extrinsic and intrinsic renal mechanisms, experiments were performed with and without renal denervation, and with and without infusions of vasopressin, norepinephrine, 17-OH-corticosterone, and aldosterone. Human and rat angiotensinogen and renin mRNA expression were also determined. In hREN without controlled renal function, urine flow and sodium excretion increased from 13 to 169 microl/min per g kidney wet weight (kwt) and from 1 to 30 micromol/min per g kwt, respectively, as renal perfusion pressure was increased from 67 to 135 mmHg. Renal blood flow (RBF) and GFR ranged between 3 to 7 and 0.9 to 1.5 ml/min per g kwt. In dTGR, pressure-natriuresis-diuresis relationships were shifted approximately 40 mmHg rightward. RBF was lower in dTGR than in hREN; GFR was not different. In dTGR with neurohormonal factors controlled, RBF was decreased and pressure-natriuresis-diuresis curves were not different compared to dTGR curves without these interventions. By light microscopy, the kidneys of these 6-wk-old dTGR and hREN rats were normal and indistinguishable. Both human and rat renin and angiotensinogen mRNA were expressed in the kidneys of dTGR. The two renin mRNA were decreased in dTGR, indicating a physiologic downregulation of renin gene expression by high BP. It is concluded that the renal pressure-natriuresis mechanism is reset toward higher pressure levels in dTGR and participates in the

  1. Changeover Trial of Azilsartan and Olmesartan Comparing Effects on the Renin-Angiotensin-Aldosterone System in Patients with Essential Hypertension after Cardiac Surgery (CHAOS Study).

    Science.gov (United States)

    Sezai, Akira; Osaka, Shunji; Yaoita, Hiroko; Arimoto, Munehito; Hata, Hiroaki; Shiono, Motomi; Sakino, Hisakuni

    2016-06-20

    Angiotensin II receptor blockers (ARBs) have been widely used to treat hypertension and large-scale clinical studies have shown various benefits. In this study, we compared olmesartan with azilsartan, the newest ARB. The subjects were outpatients who were clinically stable after cardiac surgery. Sixty patients were randomized to receive either azilsartan or olmesartan for 1 year and were switched to the other drug for the following 1 year. The primary endpoints were the levels of plasma renin activity, angiotensin II, and aldosterone. Home blood pressure exceeded 140/90 mmHg and additional antihypertensive medication was administered to 12 patients (20 episodes) in the azilsartan group versus 4 patients (4 episodes) in the olmesartan group, with the number being significantly higher in the azilsartan group. After 1 year of treatment, both angiotensin II and aldosterone levels were significantly lower in the olmesartan group than the azilsartan group. Left ventricular mass index was also significantly lower in the olmesartan group than the azilsartan group. This study showed that olmesartan reduces angiotensin II and aldosterone levels more effectively than azilsartan. Accordingly, it may be effective in patients with increased renin-angiotensin-aldosterone system activity after cardiac surgery or patients with severe cardiac hypertrophy.

  2. Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection.

    Science.gov (United States)

    Tower, Cindy M; Reyes, Morayma; Nelson, Karen; Leca, Nicolae; Kieran, Niamh; Muczynski, Kimberly; Jefferson, Jonathan A; Blosser, Christopher; Kukla, Aleksandra; Maurer, David; Chandler, Wayne; Najafian, Behzad

    2017-09-01

    Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. Currently, AMR diagnosis relies on biopsy which is an invasive procedure. A noninvasive biomarker of acute AMR could lead to early diagnosis and treatment of this condition and improve allograft outcome. Microvesicles are membrane-bound vesicles released from the cell surface after injury. We hypothesized that because AMR is associated with allograft endothelial injury and C4d deposition, plasma microvesicles positive for endothelial (CD144) marker and C4d are increased in this condition. We studied microvesicle concentration in the plasma of 95 kidney transplant patients with allograft dysfunction and compared with 23 healthy volunteers. Biopsy diagnosis and scoring was performed using Banff classification. In the 28 subjects with AMR, the density of C4d+/CD144+ microvesicles was on average 11-fold (P = 0.002) higher than transplant recipients with no AMR and 24-fold (P = 0.008) than healthy volunteers. Densities of C4d+ and C4d+/annexin V+ (C4d+/AVB+) microvesicles were also increased in AMR patients compared with no AMR and healthy subjects. C4d+/AVB+ microvesicles correlated with AMR biopsy severity. Nine patients with acute AMR that received treatment showed a mean 72% decrease (P = 0.01) in C4d+/CD144+ microvesicle concentration compared with pretreatment values. Quantification of plasma C4d+ microvesicles provides information about presence of AMR, its severity and response to treatment in transplant patients.

  3. Seasonal foraging patterns of forest-grazing Japanese Black heifers with increased plasma total antioxidant capacity.

    Science.gov (United States)

    Haga, Satoshi; Nakano, Miwa; Nakao, Seiji; Hirano, Kiyoshi; Yamamoto, Yoshito; Sasaki, Hiroyuki; Ishizaki, Hiroshi

    2016-02-01

    Forest-grazing enables the intake of high total antioxidant capacity (TAC) plants that might be beneficial for the TAC status of cattle. This study evaluated the relation between the seasonal foraging patterns of forest-grazing Japanese Black (JB) heifers or the TAC levels in shrubs and trees and the changes of plasma TAC. We examined 12 JB heifers, four each of which were allocated to forest-grazing (F), pasture-grazing, and pen-housed groups. The plasma TAC level in F heifers on July 26, August 13, 30 and September 17 were significantly higher than those on April 27 and June 4 (P < 0.05). In F group, the mean rates of foraging frequency (FF) of shrubs and trees during July 5-8 and September 13-16 were much higher than that during May 31-June 3 (P < 0.05). The rate of FF of grass significantly decreased later in the season (P < 0.05). The mean TAC levels in these shrubs and trees were higher than those in grasses, concentrates, and timothy hay. Results suggest that an important factor in the increase of plasma TAC in forest-grazing cattle might be the increased foraging of TAC-rich shrubs and trees during summer-fall.

  4. Refractory cachexia is associated with increased plasma concentrations of fentanyl in cancer patients

    Directory of Open Access Journals (Sweden)

    Suno M

    2015-05-01

    were found to possibly affect the dose-adjusted concentration of fentanyl included aspartate aminotransferase, C-reactive protein, and estimated glomerular filtration rate, when analyzed as six independent variables (multiple regression analysis, P<0.05.Conclusion: The dose-adjusted plasma concentrations of fentanyl increased with progression of cancer cachexia. Such an increase is associated with a multifactorial and systemic syndrome in cancer cachexia patients, including lower albumin, higher C-reactive protein, and impaired kidney function. In patients with cancer cachexia, we suggest that evaluation of cancer cachexia might help pain management when using a transdermal fentanyl patch in palliative care. Keywords: transdermal patch, cancer pain, LC-MS/MS

  5. The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients

    Directory of Open Access Journals (Sweden)

    Shishioh-Ikejima Nobue

    2010-08-01

    Full Text Available Abstract Background Despite extensive research, no reliable biological marker for chronic fatigue syndrome (CFS has yet been identified. However, hyperactivation of melanotrophs in the pituitary gland and increased levels of plasma alpha-melanocyte-stimulating hormone (α-MSH have recently been detected in an animal model of chronic stress. Because CFS is considered to be caused partly by chronic stress events, increased α-MSH plasma levels may also occur in CFS patients. We therefore examined α-MSH levels in CFS patients. Methods Fifty-five CFS patients, who were previously diagnosed within 10 years of with the disease, were enrolled in this study. Thirty healthy volunteers were studied as controls. Fasting bloods samples were collected in the morning and evaluated for their plasma levels of α-MSH, adrenocorticotropic hormone (ACTH, serum cortisol and dehydroepiandrosterone sulfate (DHEA-S. Mean levels of α-MSH were compared between the CFS and control groups using Welch's t test. Results The mean plasma α-MSH concentration in the CFS group (17.9 ± 1.0 pg/mL was significantly higher than that in healthy controls (14.5 ± 1.0 pg/mL, p = 0.02. However, there was a wide range of values in the CFS group. The factors correlated with the plasma α-MSH values were analyzed using Spearman's rank correlation. A negative correlation was found between the duration of the CFS and the plasma α-MSH values (p = 0.04, rs = -0.28, but no correlations with ACTH, cortisol or DHEA-S levels were identified (p = 0.55, 0.26, 0.33, respectively. The CFS patients were divided into two groups: patients diagnosed for ≤ 5 years' duration, and those diagnosed for 5-10 years' duration. They were compared with the healthy controls using one-way ANOVA and Tukey-Kramer multiple comparison tests. The mean α-MSH concentration in the ≤ 5 years group was 20.8 ± 1.2 pg/mL, which was significantly higher than that in the healthy controls (p Conclusions CFS patients with

  6. Increased Expressions of Plasma Galectin-3 in Patients with Amyotrophic Lateral Sclerosis

    Institute of Scientific and Technical Information of China (English)

    Jun Yan; Yun Xu; Li Zhang; Hui Zhao; Ling Jin; Wei-Guo Liu; Lei-Hua Weng

    2016-01-01

    Background:High expressions of galectin-3 were identified recently in the end stage of amyotrophic lateral sclerosis (ALS) patients,which suggested that immune reactivity and inflammatory mechanisms might play an important role in the pathogenesis of ALS.The purpose of this study was to investigate plasma galectin-3 levels in different groups and stages of ALS patients and the association with related clinical characteristics.Methods:A total of 51 patients with ALS and 60 normal controls (NCs) were recruited in this study.Plasma galectin-3 levels were determined using the enzyme-linked immunosorbent assay.Patients with ALS were divided into several groups according to their clinical characteristics:gender,type of disease onset,duration of disease,and clinical conditions of disease.Statistical analyses of the differences of galectin-3 levels between groups and the association with the clinical characteristics of disease were performed.Results:As compared with the NCs (201.64 [22.35-401.63] ng/ml),plasma galectin-3 levels were significantly elevated in the patients with duration >12 months (341.17 [69.12-859.22] ng/ml,P < 0.05),and the patients with limb onset of disease (254.14 [69.12-859.22] ng/ml,P < 0.05);however,no difference was found in the patients with duration ≤12 months (250.62 [109.77-334.92] ng/ml,P > 0.05),and the patients with bulbar onset of disease (251.79 [109.20-404.76] ng/ml,P > 0.05).In addition,galectin-3 levels were significantly increased in the female patients (263.27 [123.32-859.22] ng/ml,P < 0.05) while no difference was found in the male patients (220.39 [69.12-748.73] ng/ml,P > 0.05).The further statistical analyses showed that plasma galectin-3 levels were positively correlated with the duration of disease (r =0.293,P =0.037).Conclusions:Plasma galectin-3 levels were significantly increased in ALS patients with limb onset of disease,especially in ALS female patients,and positively correlated with the duration of disease

  7. Increased concentration of vasopressin in plasma of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; Warberg, J.

    1985-01-01

    The effect of essential fatty acid deficiency (EFA-D) on the plasma concentration of arginine-vasopressin (AVP) and the urinary AVP excretion was investigated. Weanling rats were fed a fat-free diet (FF-rats). Control rats received the same diet in which 6% by wt. of sucrose was replaced by arachis...... oil. After 4-6 weeks of feeding, urine and plasma were analysed for AVP, osmolality, sodium and potassium. When compared to control rats FF-rats had decreased urine volume (6.0 ± 1.6 ml/24 hr versus 11.7 ± 3.2 ml/24 hr), increased urine osmolality (2409 ± 691 mOsm/kg versus 1260 ± 434 m...

  8. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial

    NARCIS (Netherlands)

    Grubben, M.J.; Boers, G.H.; Blom, H.J.; Broekhuizen, R.; Jong, de R.; Rijt, van L.; Katan, M.B.

    2000-01-01

    Background: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations. Objective: We studied the effect of coffee consumption on plasma

  9. Ovariectomy modify local renin-angiotensin-aldosterone system gene expressions in the heart of ApoE (-/-) mice.

    Science.gov (United States)

    Borges, Celina Carvalho; Penna-de-Carvalho, Aline; Medeiros Junior, Jorge L; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos A

    2017-10-04

    The evaluation of the local Renin-Angiotensin-Aldosterone system (RAAS) gene expressions in the heart of ovariectomized (OVX) apolipoprotein E deficient mice (ApoE). Four-months old C57BL/6 female mice (wild-type, wt, n=20), and ApoE female mice (n=20), were submitted to OVX or a surgical procedure without ovary removal (SHAM) and formed four groups (n=10/group): SHAM/wt, SHAM/ApoE, OVX/wt, and OVX/ApoE. OVX led to greater body mass, plasma triglycerides (TG) and total cholesterol, and resulted in insulin resistance and altered RAAS gene expressions in the heart tissue. The gene expression of angiotensin-converting enzyme (ACE)-2 was lower in OVX/wt than in SHAM/wt (P=0.0004), Mas receptor (MASr) was lower in OVX/wt compared to SHAM/wt (P<0.0001). Also, angiotensin II receptor type 1 (AT1r) was higher in OVX/wt than in SHAM/wt (P=0.0229), and AT2r was lower in OVX/wt than in SHAM/wt (P=0.0121). OVX and ApoE deficiency showed interaction potentializing the insulin resistance, increasing TG levels and altering ACE and MASr gene expressions. ACE gene expression was higher in OVX/ApoE than in OVX/wt (P<0.0001), and MASr gene expression was lower in OVX/ApoE than in OVX/wt (P<0.0001). The impact of OVX on local RAAS cascade in the heart of ApoE deficient animals, besides the metabolic changes culminating with insulin resistance, involves an upregulation of renin, ACE, and AT1r gene expressions. The findings may contribute to clarify the mechanisms of development of postmenopausal hypertension and the link between RAAS and apolipoprotein E. Copyright © 2017. Published by Elsevier Inc.

  10. Partial characterization of hog renin purified by affinity chromatography.

    Science.gov (United States)

    Devaux, C; Ménard, J; Sicard, P; Corvol, P

    1976-05-01

    A method has been set up to purify renin on a large scale by affinity chromatography using Pepstatin, a potent inhibitor of renin, as a ligand. Pepstatin was covalently coupled to Sepharose via six different spacer 'arms'. The Sepharose-hexamethylenediamino-Pepstatin appeared to be the better derivative for renin purification even at a concentration as low as 160 nmol of Pepstatin/ml of moist gel. Renin was extracted from 100 kg of hog kidneys and semi-purified by ammonium sulfate precipitations and chromatography on DEAE-cellulose. The active fraction (48.5 g of proteins) was applied on a 500-ml affinity column. Renin was eluted in the starting buffer containing 6 M urea. Renin was purified 120-fold by the affinity chromatography step with a 79% recovery. Physico-chemical characterization of highly purified renin was performed. Isoelectrofocusing on a pH gradient from 3 to 6 showed a major peak with an isoelectric point (pI) of 4.95 and a minor peak (pI = 4.70). Polyacrylamide gel electrophoresis, pH 7.8, at different gel concentrations, showed a single peak of renin activity which was found in the major protein band. Molecular size estimated on agarose-acrylamide gel filtration was 40 000. All these physical parameters were similar before and after purification.

  11. Urinary renin and angiotensinogen in type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Lu, Xifeng; Rossing, Peter;

    2013-01-01

    Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade....

  12. Plasma Irisin Modestly Increases during Moderate and High-Intensity Afternoon Exercise in Obese Females

    Science.gov (United States)

    Winn, Nathan C.; Grunewald, Zachary I.; Liu, Ying; Heden, Timothy D.; Nyhoff, Lauren M.; Kanaley, Jill A.

    2017-01-01

    Background and Purpose Irisin is an exercise-responsive myokine that has been proposed to exert anti-obesity benefits; yet its response during exercise in obese women is not described. This study characterized plasma irisin levels during a single bout of afternoon isocaloric-exercise of different intensities (moderate- vs high-intensity) in obese females. Methods Eleven obese females participated in 3 randomized study days beginning at 1600h: 1) no exercise (NoEx), 2) moderate exercise (ModEx; 55%VO2max) and 3) high intensity interval exercise (IntEx; 4 min (80%VO2max)/3 min (50% VO2max). Frequent blood samples were analyzed for glucose and lactate (whole-blood), and insulin, c-peptide, glucagon, and irisin (plasma) throughout 190 min of testing. Results Plasma irisin increased above baseline during ModEx and IntEx (P0.05). Peak irisin levels during ModEx and IntEx exercise were 11.9± 3.4% and 12.3 ± 4.1% relative to baseline (Pexercise intensities (P>0.05). Irisin levels remained elevated above resting for 125 minutes post-exercise during ModEx, whereas levels returned to baseline within 15 minutes post-exercise during IntEx. Similarly, no associations were found between plasma irisin levels and circulating lactate, glucose, insulin, c-peptide, or glucagon among study days (P>0.05). However, there was an inverse association between basal irisin and lean mass (r = -0.70, P = 0.01). Conclusion A single bout of moderate and high intensity afternoon exercise induces modest increases in circulating irisin concentrations during exercise; however the regulation post-exercise appears to be dimorphic between exercise intensity in obese females. Future studies are needed to compare morning and afternoon exercise on irisin secretion. PMID:28125733

  13. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Directory of Open Access Journals (Sweden)

    Karine M Yamashita

    2014-05-01

    Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

  14. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Science.gov (United States)

    Yamashita, Karine M; Alves, André F; Barbaro, Katia C; Santoro, Marcelo L

    2014-05-01

    Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering bleeding manifestations in severely-envenomed patients.

  15. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork.

    Science.gov (United States)

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors.

  16. Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

    Directory of Open Access Journals (Sweden)

    Karine M Yamashita

    2014-05-01

    Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

  17. Streptococcal Serum Opacity Factor Increases Hepatocyte Uptake of Human Plasma High Density Lipoprotein-Cholesterol1

    Science.gov (United States)

    Gillard, Baiba K.; Rosales, Corina; Pillai, Biju K.; Lin, Hu Yu; Courtney, Harry S.; Pownall, Henry J.

    2010-01-01

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM), that contains the cholesterol esters (CE) of up to ~400,000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. [3H]CE uptake by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was respectively 2.4 and 4.5 times faster than from control HDL. CERM-[3H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[3H]CE uptake by both receptors. RAP and heparin inhibit CERM-[3H]CE but not HDL-[3H]CE uptake thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  18. Increased plasma retinol binding protein 4 levels in patients with inflammatory cardiomyopathy.

    Science.gov (United States)

    Bobbert, Peter; Weithäuser, Alice; Andres, Janin; Bobbert, Thomas; Kühl, Uwe; Schultheiss, Heinz Peter; Rauch, Ursula; Skurk, Carsten

    2009-12-01

    Chronic heart failure (CHF) is associated with a higher risk for diabetes mellitus. Retinol binding protein 4 (RBP 4) is an adipose tissue-derived protein with pro-diabetogenic effects. A complete understanding of the association of CHF and insulin resistance remains elusive. The purpose of this study was to examine the relationship between CHF and diabetes mellitus. Plasma levels of RBP 4, insulin, and interleukins (IL) 2, 8, and 10, were assessed in patients with dilated cardiomyopathy (DCM, n = 53), dilated inflammatory cardiomyopathy (DCMi, n = 54), and controls (n = 20). In addition, a possible mechanism of RBP 4 regulation was examined in adipocytes in vitro. Plasma levels of RBP 4 and insulin were measured by a specific ELISA. Interleukin concentrations were obtained by multiplex ELISA. Cell culture with 3T3-L1 adipocytes was performed to measure RBP 4 mRNA expression after stimulation with IL-8. RBP 4 levels were significantly increased in patients with DCMi (52.95 +/- 20.42 microg/mL) compared with DCM (35.54 +/- 23.08 microg/mL) and the control group (27.3 +/- 18.51 microg/mL). RBP 4 was positively correlated with IL-8 (r=0.416, P < 0.05) in human plasma in patients with DCMi. Moreover, increased insulin resistance was observed in patients with DCMi compared with the control and DCM groups. In vitro, IL-8 induced a significant upregulation of RBP 4 mRNA expression in adipocytes. Elevated RBP 4 plasma concentrations, induced by IL-8, might be one mechanism leading to a higher incidence of diabetes in patients with DCMi.

  19. The Studies on Theraputic Effects of Benazapril and Bisoprolol Combinationin in Hypertensive Patients and Plasma Renin Activity%贝那普利联合比索洛尔的降压疗效与血浆肾素水平的相关研究

    Institute of Scientific and Technical Information of China (English)

    扈晓霞; 袁兰所; 冯亚宾; 陈茗莉; 赵志华; 王艳玲; 郑群

    2011-01-01

    Objective To explore the relationship between plasma renin activity ( PRA ) and theraputic effects of henazapril and bisoprolol combination in essential hypertensive patients finding the effect screening PRA tangent point. Methods A total of 200 patients with mild to moderate hypertension without severe organic diseases at cardiovascular clinic in Harrison International Peace Hospital from Jan. ,2007 to Oct.,2010.100 males and 100 females,aged≥6 years at an average of 48 yrs, were enrolled in the first-phase single-blind study,i. e. a 3-week treatment of henazapril 10mg QD,the patients with blood pressure meeting the standard (<140/90 mm Hg ) were out; the left were then randomly assigned to benazapril 10 mg QD group( 75 cases ) , benazapril 10 mg QD plus bisoprolol 5 mg QD group ( 75 cases ) in double-blind, randomized study. SBP and DBP were recorded before and after the double-blind therapy. PRA was detected before single-blind study and low-PRA level hypertension patients were excluded. Results Compared with their haseline values, blood pressure reduction was more prominent in patients in henazapril and bisoprolol combinationin group,SBP:[ ( 130. 0 ±13.0 ) mm Hg vs ( 125. 9±9. 7 ) mm Hg ],P <0. 05. DBP :[ ( 89. 7 ± 8. 6 ) mm Hg vs ( 84.0± 7. 9 ) mm Hg ],P <0. 05 . Receiver operating characteristic curve( PRA)> 2. 69μg/( h · min ) was the best tangent point above which the effect of henazapril and bisoprolol combination was more significant in high PRA hypertensive patients. The prediction sensitivity and specificity is 100% and 94. 8% respectively. Conclusion The theraputic effects of benazapril and bisoprolol comhination in hypertensive patients is better than benazapril dosage increase. PRA > 2. 69 μg/( h . min ) is the best effective tangent point for high PRA hypertension.%目的 探讨贝那普利的降压疗效与血浆肾素水平的相关性,寻找原发性高血压的血浆肾素水平的疗效筛选切点.方法 选取2007年1

  20. The Protective Arm of the Renin Angiotensin System (RAS)

    DEFF Research Database (Denmark)

    The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which...... will become of major medical importance in the near future. Focusing on recent research, The Protective Arm of the Renin Angiotensin System presents a host of new experimental studies on specific components of the RAS, namely angiotensin AT2 receptors (AT2R), the angiotensin (1-7) peptide with its receptor...... understanding of the protective side of the Renin Angiotensin System (RAS) involving angiotensin AT2 receptor, ACE2, and Ang(1-7)/Mas receptor Combines the knowledge of editors who pioneered research on the protective renin angiotensin system including; Dr. Thomas Unger, one of the founders of AT2 receptor...

  1. Mammary renin-angiotensin system-regulating aminopeptidase activities are modified in rats with breast cancer.

    Science.gov (United States)

    del Pilar Carrera, Maria; Ramírez-Expósito, Maria Jesus; Mayas, Maria Dolores; García, Maria Jesus; Martínez-Martos, Jose Manuel

    2010-12-01

    Angiotensin II in particular and/or the local renin-angiotensin system in general could have an important role in epithelial tissue growth and modelling; therefore, it is possible that it may be involved in breast cancer. In this sense, previous works of our group showed a predominating role of angiotensin II in tumoral tissue obtained from women with breast cancer. However, although classically angiotensin II has been considered the main effector peptide of the renin-angiotensin system cascade, several of its catabolism products such as angiotensin III and angiotensin IV also possess biological functions. These peptides are formed through the activity of several proteolytic regulatory enzymes of the aminopeptidase type, also called angiotensinases. The aim of this work was to analyse several specific angiotensinase activities involved in the renin-angiotensin system cascade in mammary tissue from control rats and from rats with mammary tumours induced by N-methyl-nitrosourea (NMU), which may reflect the functional status of their target peptides under the specific conditions brought about by the tumoural process. The results show that soluble and membrane-bound specific aspartyl aminopeptidase activities and membrane-bound glutamyl aminopeptidase activity increased in mammary tissue from NMU-treated animals and soluble aminopeptidase N and aminopeptidase B activities significantly decreased in mammary tissue from NMU-treated rats. These changes support the existence of a local mammary renin-angiotensin system and that this system and its putative functions in breast tissue could be altered by the tumour process, in which we suggest a predominant role of angiotensin III. All described data about the renin-angiotensin system in mammary tissue support the idea that it must be involved in normal breast tissue functions, and its disruption could be involved in one or more steps of the carcinogenesis process.

  2. Scaling of surface-plasma reactors with a significantly increased energy density for NO conversion.

    Science.gov (United States)

    Malik, Muhammad Arif; Xiao, Shu; Schoenbach, Karl H

    2012-03-30

    Comparative studies revealed that surface plasmas developing along a solid-gas interface are significantly more effective and energy efficient for remediation of toxic pollutants in air than conventional plasmas propagating in air. Scaling of the surface plasma reactors to large volumes by operating them in parallel suffers from a serious problem of adverse effects of the space charges generated at the dielectric surfaces of the neighboring discharge chambers. This study revealed that a conductive foil on the cathode potential placed between the dielectric plates as a shield not only decoupled the discharges, but also increased the electrical power deposited in the reactor by a factor of about forty over the electrical power level obtained without shielding and without loss of efficiency for NO removal. The shield had no negative effect on efficiency, which is verified by the fact that the energy costs for 50% NO removal were about 60 eV/molecule and the energy constant, k(E), was about 0.02 L/J in both the shielded and unshielded cases.

  3. Increase in plasma platelet-activating factor levels in enterally fed preterm infants.

    Science.gov (United States)

    MacKendrick, W; Hill, N; Hsueh, W; Caplan, M

    1993-01-01

    Because platelet-activating factor (PAF) has been implicated in the pathogenesis of neonatal necrotizing enterocolitis (NEC), we designed a prospective study to examine plasma PAF levels during the first 14 days of feeding in a population of neonates of less than 32 weeks gestation. We found that significantly more patients had detectable plasma PAF levels on days 3 and 14 of feeding when compared to their prefeeding levels (7% on day 0 vs. 26% at day 3, p = 0.04; none on day 0 vs. 18.5% at day 14, p = 0.01). This finding could not be explained by decreased plasma activity of acetylhydrolase, the PAF breakdown enzyme, spontaneous endotoxinemia or a maturational effect. None of the infants who developed detectable PAF levels after feedings were begun went on to develop NEC. We conclude that our findings may reflect increased intestinal PAF production with the provision of feedings to some premature infants. However, this phenomenon by itself does not appear to be a sufficient condition for the subsequent development of NEC.

  4. Plasma proteome coverage is increased by unique peptide recovery from sodium deoxycholate precipitate.

    Science.gov (United States)

    Serra, Aida; Zhu, Hongbin; Gallart-Palau, Xavier; Park, Jung Eun; Ho, Hee Haw; Tam, James P; Sze, Siu Kwan

    2016-03-01

    The ionic detergent sodium deoxycholate (SDC) is compatible with in-solution tryptic digestion and LC-MS/MS-based shotgun proteomics by virtue of being easy to separate from the peptide products via precipitation in acidic buffers. However, it remains unclear whether unique human peptides co-precipitate with SDC during acid treatment of complex biological samples. In this study, we demonstrate for the first time that a large quantity of unique peptides in human blood plasma can be co-precipitated with SDC using an optimized sample preparation method prior to shotgun proteomic analysis. We show that the plasma peptides co-precipitated with SDC can be successfully recovered using a sequential re-solubilization and precipitation procedure, and that this approach is particularly efficient at the extraction of long peptides. Recovery of peptides from the SDC pellet dramatically increased overall proteome coverage (>60 %), thereby improving the identification of low-abundance proteins and enhancing the identification of protein components of membrane-bound organelles. In addition, when we analyzed the physiochemical properties of the co-precipitated peptides, we observed that SDC-based sample preparation improved the identification of mildly hydrophilic/hydrophobic proteins that would otherwise be lost upon discarding the pellet. These data demonstrate that the optimized SDC protocol is superior to sodium dodecyl sulfate (SDS)/urea treatment for identifying plasma biomarkers by shotgun proteomics.

  5. Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial.

    Science.gov (United States)

    McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John

    2017-05-08

    Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m(2)) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group (P=0.83), -4 (-16 to 9) in the allopurinol group (P=0.32), and 1 (-21 to 17) in the placebo group (P=0.96), with no significant treatment effect (P=0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid (P=0.43), -0.4±6.1 with allopurinol (P=0.76), and 0.5±6.0 with placebo (P=0.65); there was no significant treatment effect (P=0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney-specific or

  6. The renin-angiotensin system and its blockers

    Directory of Open Access Journals (Sweden)

    Igić Rajko

    2014-01-01

    Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

  7. Engagement of renin-angiotensin system in prostate cancer.

    Science.gov (United States)

    Uemura, Hiroji; Hoshino, Koji; Kubota, Yoshinobu

    2011-05-01

    Angiotensin II (Ang-II) plays a role not only as a vasoconstrictor in controlling blood pressure and electrolyte and fluid homeostasis, but also as a mitogenic factor through the Ang-II type-1 (AT1) receptor in cardiovascular cells. Since a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors has been reported, the molecular mechanisms of the renin-angiotensin system (RAS) in cancer cells have been elucidated. Interestingly, there is increasing evidence that the RAS is implicated in the development of prostate cancer. As previously reported, AT1 receptor blockers (ARBs), a class of antihypertensive agent, have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review highlights that the RAS plays a potential role in various aspects of prostate cancer, and ARBs could be useful for treatment of prostate cancer or its chemoprevention.

  8. High potassium promotes mutual interaction between (pro)renin receptor and the local renin-angiotensin-aldosterone system in rat inner medullary collecting duct cells.

    Science.gov (United States)

    Xu, Chuanming; Fang, Hui; Zhou, Li; Lu, Aihua; Yang, Tianxin

    2016-10-01

    (Pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD) with unclear functional implication. It is not known whether CD PRR is regulated by high potassium (HK). Here, we aimed to investigate the effect of HK on PRR expression and its role in regulation of aldosterone synthesis and release in the CD. In primary rat inner medullary CD cells, HK augmented PRR expression and soluble PPR (sPRR) release in a time- and dose-dependent manner, which was attenuated by PRR small interfering RNA (siRNA), eplerenone, and losartan. HK upregulated aldosterone release in parallel with an increase of CYP11B2 (cytochrome P-450, family 11, subfamily B, polypeptide 2) protein expression and upregulation of medium renin activity, both of which were attenuated by a PRR antagonist PRO20, PRR siRNA, eplerenone, and losartan. Similarly, prorenin upregulated aldosterone release and CYP11B2 expression, both of which were attenuated by PRR siRNA. Interestingly, a recombinant sPRR (sPRR-His) also stimulated aldosterone release and CYP11B2 expression. Taken together, we conclude that HK enhances a local renin-angiotensin-aldosterone system (RAAS), leading to increased PRR expression, which in turn amplifies the response of the RAAS, ultimately contributing to heightened aldosterone release.

  9. Enzyme-inducing anticonvulsants increase plasma clearance of dexmedetomidine: a pharmacokinetic and pharmacodynamic study.

    Science.gov (United States)

    Flexman, Alana M; Wong, Harvey; Riggs, K Wayne; Shih, Tina; Garcia, Paul A; Vacas, Susana; Talke, Pekka O

    2014-05-01

    Dexmedetomidine is useful during mapping of epileptic foci as it facilitates electrocorticography unlike most other anesthetic agents. Patients with seizure disorders taking enzyme-inducing anticonvulsants appear to be resistant to its sedative effects. The objective of the study was to compare the pharmacokinetic and pharmacodynamic profile of dexmedetomidine in healthy volunteers with volunteers with seizure disorders receiving enzyme-inducing anticonvulsant medications. Dexmedetomidine was administered using a step-wise, computer-controlled infusion to healthy volunteers (n = 8) and volunteers with seizure disorders (n = 8) taking phenytoin or carbamazapine. Sedation and dexmedetomidine plasma levels were assessed at baseline, during the infusion steps, and after discontinuation of the infusion. Sedation was assessed by using the Observer's Assessment of Alertness/Sedation Scale, Ramsay Sedation Scale, and Visual Analog Scale and processed electroencephalography (entropy) monitoring. Pharmacokinetic analysis was performed on both groups, and differences between groups were determined using the standard two-stage approach. A two-compartment model was fit to dexmedetomidine concentration-time data. Dexmedetomidine plasma clearance was 43% higher in the seizure group compared with the control group (42.7 vs. 29.9 l/h; P = 0.007). In contrast, distributional clearance and the volume of distribution of the central and peripheral compartments were similar between the groups. No difference in sedation was detected between the two groups during a controlled range of target plasma concentrations. This study demonstrates that subjects with seizure disorders taking enzyme-inducing anticonvulsant medications have an increased plasma clearance of dexmedetomidine as compared with healthy control subjects.

  10. Effects of gender on screening value of aldosterone-renin ratio for primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Ye-qiong SONG

    2017-02-01

    Full Text Available Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR for primary aldosteronism (PA. Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC was conducted to evaluate the best cut-off value. Results The plasma aldosterone concentration (PAC, serum sodium and ARR were much higher, but the plasma rennin activity (PRA, serum potassium and BMI were much lower in PA patients than in EH patients (P0.05. The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC was 0.968, the sensitivity and specificity was 92.44% and 93.08%, and the Youden index (YI was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specificity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specificity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specificity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the official value recommended by guidelines. Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher. DOI: 10.11855/j.issn.0577-7402.2017.01.10

  11. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine

    2016-01-01

    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed...... with 13% energy from cheese or butter. Results After 6 weeks of intervention cheese resulted in higher amounts of calcium excreted in feces compared to butter. However, no difference was observed in fecal bile acid output despite lower serum total, LDL and HDL cholesterol concentrations observed...

  12. Continuous reduction of plasma paraoxonase activity with increasing dialysis vintage in hemodialysis patients

    DEFF Research Database (Denmark)

    Henning, Bernhard F; Holzhausen, Helge; Tepel, Martin

    2010-01-01

    Plasma paraoxonase (PON) is an enzyme that hydrolyzes organic phosphate and aromatic carboxylic acid esters. Reduced activity is associated with early events of atherogenesis. The relevance of PON phenotypes is not well characterized in hemodialysis patients. In a cross-sectional study we measured...... phenotypes. 74% of hemodialysis patients showed PON phenotype 1, 21% PON phenotype 2, and 5% PON phenotype 3. Compared to hemodialysis patients with PON 1, patients with PON 2 or 3 showed higher conversion rates for 4-nitrophenylacetate. We observed a significant reduction of PON ratio with increasing...

  13. Increased plasma concentration of serum amyloid P component in centenarians with impaired cognitive performance

    DEFF Research Database (Denmark)

    Nybo, M; Olsen, H; Jeune, B;

    1998-01-01

    these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p ... higher SAP concentration (60.2 microg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4+/-9.3 microg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive...... performance had significantly increased plasma concentrations of SAP, while the values for cognitive intact centenarians were within the normal range....

  14. Plasma levels of soluble tumour necrosis factor receptors are increased in coal miners with pneumoconiosis.

    Science.gov (United States)

    Schins, R P; Borm, P J

    1995-10-01

    Among other cytokines, tumour necrosis factor (TNF)-alpha is considered to play a key role in the development of mineral dust related fibrosis. Previously, we showed that ex-vivo release of TNF by peripheral blood monocytes is a marker for progression of coal workers' pneumoconiosis (CWP). Since soluble TNF receptors (sTNF-Rs) are believed to play an important regulatory role in systemic effects of TNF, we measured plasma levels of sTNF-R55 and sTNF-R75 in coal miners with (n = 28) or without (n = 76) CWP and in nonexposed controls (n = 29). sTNF-R75 levels were significantly increased in miners with CWP (2.09 +/- 0.44 ng.mL-1) versus the nonexposed controls (1.86 +/- 0.23 ng.mL-1). Neither sTNF-R55 nor sTNF-R75 were related to exposure, stage of pneumoconiosis, smoking, or (spontaneous or ex-vivo induced) monocyte TNF-release. sTNF-R55 was increased in subjects with medication (especially those using cardiovascular drugs); upon exclusion of these subjects, sTNF-R55 was found also to be significantly increased in CWP. In conclusion, bearing in mind a confounding effect of medication, soluble TNF receptors are elevated in plasma of retired miners with coal workers' pneumoconiosis. These observations further support the important role of TNF-mediated pathways in the pathogenesis of mineral dust related fibrosis.

  15. INCREASE OF THE OPERATIONAL PROPERTIES OF WELD AND PLASMA COATINGS USING NANOPOWDERS

    Directory of Open Access Journals (Sweden)

    Andrii Chornyi

    2016-07-01

    Full Text Available In this work, studies concerning determination of the oxide nanoparticles effect on structure and performance of the welds and plasma coatings were conducted. Ways of introducing nanodisperse refractory powders to the weld pool and how to cover with the deactivation of nanoparticles powder were determined. Introducing of the nanoparticles in the molten pool during the deposition and the coating was carried out by preparing a powder mixture by mechano-chemical processing in special high-energy intensive planetary mills. Structural studies of welds with nanooxides additives in the weld pool showed the formation of milled dispersed structure with microhardness 264-304 MPa. Statistical mean value of the number of non-metallic inclusions was defined. Mechanical testing of welds showed growth of the yield as well as tensile strength, when titanium and aluminum nanooxides were introduced into the weld pool. The most significant effect on these parameters has aluminum nanooxide in an amount of 0.5 vol.%, increasing the yield strength by 49 % and the tensile strength by 23 %. The toughness is mostly affected by titanium oxide in an amount of 1 vol.%., increasing its value by about 2 times. In turn, the introduction of alumina nanopowder in quantity 1,5 vol.% into the plasma coatings allowed to reduce friction and increase wear resistance of coatings by 2-3 times.

  16. Volume regulatory hormones and plasma volume in pregnant women with sickle cell disorder

    Directory of Open Access Journals (Sweden)

    Bosede B Afolabi

    2016-09-01

    Full Text Available Background: Sickle cell disease (haemoglobin SS (HbSS mainly affects those of West African origin and is associated with hypervolaemia. Plasma volume rises by up to 50% in normal pregnancy but was previously found to be paradoxically contracted in late sickle cell pregnancy. The renin–angiotensin–aldosterone system is activated very early in human pregnancy to support the plasma volume expansion. We hypothesised that activation of the renin–angiotensin–aldosterone system would be blunted in pregnant women with sickle cell disease. Materials and methods: We measured plasma volume and concentrations of plasma renin, angiotensinogen, aldosterone and other volume-related hormones in a cross-sectional study of pregnant and non-pregnant Nigerian women with HbSS or HbAA. Results: Plasma volume was higher in non-pregnant HbSS than HbAA women, but had not risen by 16 weeks, unlike plasma volume in HbAA women. The concentration of plasma renin also rose significantly less by 16 weeks in HbSS; angiotensinogen and aldosterone concentrations increased. Conclusions: The lower plasma renin concentration at 16 weeks with HbSS could be either primary or secondary to vasoconstriction related to inadequate vasodilator activity. The contracted plasma volume might then stimulate aldosterone synthesis by non-angiotensin II dependent stimulation. Studies of vasodilators such as nitric oxide, vasodilator eicosanoids or the PlGF/VEGF/sFlT-1 axis in pregnant HbSS and HbAA women will test this hypothesis.

  17. Upregulation of glycolytic enzymes, mitochondrial dysfunction and increased cytotoxicity in glial cells treated with Alzheimer's disease plasma.

    Directory of Open Access Journals (Sweden)

    Tharusha Jayasena

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder associated with increased oxidative stress and neuroinflammation. Markers of increased protein, lipid and nucleic acid oxidation and reduced activities of antioxidant enzymes have been reported in AD plasma. Amyloid plaques in the AD brain elicit a range of reactive inflammatory responses including complement activation and acute phase reactions, which may also be reflected in plasma. Previous studies have shown that human AD plasma may be cytotoxic to cultured cells. We investigated the effect of pooled plasma (n = 20 each from healthy controls, individuals with amnestic mild cognitive impairment (aMCI and Alzheimer's disease (AD on cultured microglial cells. AD plasma and was found to significantly decrease cell viability and increase glycolytic flux in microglia compared to plasma from healthy controls. This effect was prevented by the heat inactivation of complement. Proteomic methods and isobaric tags (iTRAQ found the expression level of complement and other acute phase proteins to be altered in MCI and AD plasma and an upregulation of key enzymes involved in the glycolysis pathway in cells exposed to AD plasma. Altered expression levels of acute phase reactants in AD plasma may alter the energy metabolism of glia.

  18. Slowing of Magnetic Reconnection Concurrent with Weakening Plasma Inflows and Increasing Collisionality in Strongly Driven Laser-Plasma Experiments.

    Science.gov (United States)

    Rosenberg, M J; Li, C K; Fox, W; Zylstra, A B; Stoeckl, C; Séguin, F H; Frenje, J A; Petrasso, R D

    2015-05-22

    An evolution of magnetic reconnection behavior, from fast jets to the slowing of reconnection and the establishment of a stable current sheet, has been observed in strongly driven, β≲20 laser-produced plasma experiments. This process has been inferred to occur alongside a slowing of plasma inflows carrying the oppositely directed magnetic fields as well as the evolution of plasma conditions from collisionless to collisional. High-resolution proton radiography has revealed unprecedented detail of the forced interaction of magnetic fields and super-Alfvénic electron jets (V_{jet}∼20V_{A}) ejected from the reconnection region, indicating that two-fluid or collisionless magnetic reconnection occurs early in time. The absence of jets and the persistence of strong, stable magnetic fields at late times indicates that the reconnection process slows down, while plasma flows stagnate and plasma conditions evolve to a cooler, denser, more collisional state. These results demonstrate that powerful initial plasma flows are not sufficient to force a complete reconnection of magnetic fields, even in the strongly driven regime.

  19. Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake by Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Dubey, Raghvendra K; Leeners, Brigitte; Imthurn, Bruno; Merki-Feld, Gabriele Susanne; Rosselli, Marinella

    2017-09-26

    We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound (3) H-propranolol and (14) C-warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1-1000 μM) increased the free fraction (fu) of both albumin and alpha-acid glycoprotein bound drugs in a concentration-dependent manner (p < 0.01). Moreover, piperine (10 μM) increased the uptake of (3) H-propranolol and (14) C-warfarin by BMECs (p < 0.01). In conclusion, our findings provide the first evidence that piperine displaces plasma bound drugs from both albumin and alpha-acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Extracellular matrix protein fibulin-1 plasma levels are associated with increased cardiovascular risk in chronic kidney disease

    DEFF Research Database (Denmark)

    Scholze, Alexandra

    INTRODUCTION AND AIMS: Fibulin-1 is one of the few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease in patients with chronic kidney disease. METHODS: Plasma fibulin-1...... of plasma fibulin-1. CONCLUSIONS: Increased plasma fibulin-1 levels were associated with impaired kidney function and diabetes. Fibulin-1 levels were also associated with hemodynamic cardiovascular risk markers. We conclude, that fibulin-1 is involved in the pathogenesis of cardiovascular disease observed...

  1. Increasing in activity and plasma concentration of matrix metalloproteinase-9 in metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Morteza Sadeghi1

    2009-01-01

    Full Text Available (Received 30 March, 2009 ; Accepted 22 July, 2009AbstractBackground and purpose: Matrix metalloproteinase are a family of proteolytic enzymes that have specific functions in digestion of cells cohesive extra cellular matrix and also, increasing metastasis behavior of acute human tumors. It has been reported that MMPs in two forms, namely proenzyme and active enzyme in biological samples. It is distinguished that among this family, (MMP-9 Matrix Metalloproteinase-9 has function in both initiation and invasion steps of breast cancer. In our previous study, we reported a correlation between C/T polymorphism at promoter region of this gene and metastasis step of breast cancer.Considering few findings regarding the relationship between the active form of this enzyme and occurrence of cancer, and also the correlation between active form and allelic genotype of persons, in this study we decided to do a parallel study on measurement of active plasma MMP-9 and its relationship with allelic genotype of breast cancer patients.Materials and methods: After analysis of data, we found that concentration of active MMP-9 has a significant difference in breast cancer patients in comparison with control group, as the concentration of active form of this enzyme was less in control group than the breast cancer patients group (0.7 ng and 1.7 ng respectively. Thus, the level of active MMP-9 showed a significant increase in persons with CT and TT genotypes in comparison with CC genotype (1.5 folds.Results: The present data suggest the concentration of active MMP-9 in breast cancer patients has significantly increased in comparison with the control group and the increased in plasma level of this enzyme is related with the existence of T allele at this gene promoter and also in progression of breast cancer in these patients. We can use the active plasma level of this enzyme or the existence of T allele as a diagnostic tool for discriminating subgroups of breast cancer

  2. Using plasma renin concentration to screen primary aldosteronism in hypertensive patients and to observe the effect of posture%应用血浆肾素浓度进行原发性醛固酮增多症筛查的评价及不同体位筛查效率的比较

    Institute of Scientific and Technical Information of China (English)

    鄞国书; 张少玲; 吴木潮; 黎锋; 徐明彤; 陈黎红; 程桦; 严励

    2010-01-01

    目的 比较应用血浆醛固酮/血浆肾素活性(PAC/PRA,ARR)及PAC/血浆肾素浓度(PAC/PRC,AARR)进行原发性醛固酮增多症(PA)筛查的特异性和敏感性差异,评价测定血浆肾素浓度在PA筛查中的价值,并比较不同体位下AARR的筛查效率.方法 (1)对28例通过确诊试验或手术病理证实的PA患者和51例原发性高血压患者测定卧位、立位1 h和立位2 h的AARR,比较不同体位和时间下测定的AARR在PA筛查中的效率.(2)对31例PA患者、242例原发性高血压患者及145名健康志愿者测定立位1h PAC、PRA和PRC,计算ARR和AARR,通过构建ARR和AARR对诊断PA的受试者工作特征曲线(ROC),比较两者在PA筛查中的敏感性和特异性,探讨AARR在筛查PA中的价值,并确定最佳的切点.结果 (1)卧位、立位1 h和立位2 h AARR的ROC曲线下面积分别是0.950(95%CI 0.906~0.994,P<0.01)、0.979(95%CI 0.956~1.000,P<0.01)和0.917(95%CI0.856~0.979,P<0.01).立位1 h AARR具有最高的筛查效率.(2)立位1 h Log-PRA和Log-PRC相关系数为0.705,Log-ARR和Log-AARR的相关系数为0.788.ARR和AARR的ROC曲线下面积分别为0.998(95%CI0.981~1.000,P<0.01)和0.957(95%CI0.929~0.985,P<0.01).AARR的最佳切点为42.36 ng·dl-1/ng·dl-1,其敏感性和特异性分别达到87.10%和93.75%.结论 应用AARR和ARR在高血压患者中进行PA的诊断效果相当,以立位1 h测定的AARR具有最佳的筛查效率,最佳切点为42.36 ng·dl-1/ng·dl-1.%Objective Plasma renin concentration (PRC) offers advantages in processing and standardization as compared with plasma renin activity (PRA). The aim of the study is to compare the sensitivity and specificity of plasma aldosterone concentration ( PAC)/PRA (ARR) and PAC/PRC (AARR) in screening primary aldosteronism ( PA ) in hypertensive patients and to observe the influence of different postures on PRC and AARR. Method ( 1 ) PAC and PRC in the supine position and after 1-hour and 2-hour upright posture were

  3. Altered Antioxidant Status and Increased Lipid Per-Oxidation in Seminal Plasma of Tunisian Infertile Men

    Science.gov (United States)

    Atig, Fatma; Raffa, Monia; Ali, Habib Ben; Abdelhamid, Kerkeni; Saad, Ali; Ajina, Mounir

    2012-01-01

    Human seminal plasma is a natural reservoir of antioxidants that protect spermatozoa from oxidative damages. There is evidence in literature supports the fact that impairments in seminal antioxidant and lipid per-oxidation status play important roles in the physiopathology of male infertility. Our present study forms the first one which was carried out in Tunisia. We evaluated the antioxidant status in the seminal plasma of 120 infertile men programmed to In Vitro Fertilization (IVF) for the first tentative. Patients were characterized by an idiopathic infertility. They were divided into three groups: normozoospermics who were considered as controls (n=40), asthenozoospermics (Astheno; n=45) and oligoasthenoteratozoospermics (OAT; n=35). Seminal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the levels of glutathione (GSH), zinc (Zn) and malondialdehyde (MDA) were measured. With the significant increase of the seminal activities of SOD and GPX in normozoospermics group, there were positive correlations observed between this enzymes and sperm quality. Also, significant elevated rates of seminal zinc and GSH were observed in control group, but there was contradictory associations reflecting the effects of these antioxidants on semen parameters. However, we noted significant increase of MDA levels in groups with abnormal seminogram. We showed negative associations between this per-oxidative marker and sperm parameters. These results obviously suggested that impairment on seminal antioxidants is an important risk factor for low sperm quality associated to idiopathic infertility and as a result can lead to poor IVF outcome. PMID:22211112

  4. Decreased Fibroblast and Increased Osteoblast Functions on Ionic Plasma Deposited Nanostructured Ti Coatings

    Directory of Open Access Journals (Sweden)

    Storey Dan

    2007-01-01

    Full Text Available AbstractBioactive coatings are in high demand to control cellular functions for numerous medical devices. The objective of this in vitro study was to characterize for the first time fibroblast (fibrous scar tissue forming cells adhesion and proliferation on an important polymeric biomaterial (silicone coated with titanium using a novel ionic plasma deposition (IPD process. Fibroblasts are one of the first anchorage-dependent cells to arrive at an implant surface during the wound healing process. Persistent excessive functions of fibroblasts have been linked to detrimental fibrous tissue formation which may cause implant failure. The IPD process creates a surface-engineered nanostructure (with features usually below 100 nm by first using a vacuum to remove all contaminants, then guiding charged metallic ions or plasma to the surface of a medical device at ambient temperature. Results demonstrated that compared to currently used titanium and uncoated silicone, silicone coated with titanium using IPD significantly decreased fibroblast adhesion and proliferation. Results also showed competitively increased osteoblast (bone-forming cells over fibroblast adhesion on silicone coated with titanium; in contrast, osteoblast adhesion was not competitively increased over fibroblast adhesion on uncoated silicone or titanium controls. In this manner, this study strongly suggests that IPD should be further studied for biomaterial applications in which fibrous tissue encapsulation is undesirable (such as for orthopedic implants, cardiovascular components, etc..

  5. Altered Antioxidant Status and Increased Lipid Per-Oxidation in Seminal Plasma of Tunisian Infertile Men

    Directory of Open Access Journals (Sweden)

    Fatma Atig, Monia Raffa, Habib Ben Ali, Kerkeni Abdelhamid, Ali Saad, Mounir Ajina

    2012-01-01

    Full Text Available Human seminal plasma is a natural reservoir of antioxidants that protect spermatozoa from oxidative damages. There is evidence in literature supports the fact that impairments in seminal antioxidant and lipid per-oxidation status play important roles in the physiopathology of male infertility. Our present study forms the first one which was carried out in Tunisia. We evaluated the antioxidant status in the seminal plasma of 120 infertile men programmed to In Vitro Fertilization (IVF for the first tentative. Patients were characterized by an idiopathic infertility. They were divided into three groups: normozoospermics who were considered as controls (n=40, asthenozoospermics (Astheno; n=45 and oligoasthenoteratozoospermics (OAT; n=35. Seminal activities of superoxide dismutase (SOD and glutathione peroxidase (GPX and the levels of glutathione (GSH, zinc (Zn and malondialdehyde (MDA were measured. With the significant increase of the seminal activities of SOD and GPX in normozoospermics group, there were positive correlations observed between this enzymes and sperm quality. Also, significant elevated rates of seminal zinc and GSH were observed in control group, but there was contradictory associations reflecting the effects of these antioxidants on semen parameters. However, we noted significant increase of MDA levels in groups with abnormal seminogram. We showed negative associations between this per-oxidative marker and sperm parameters. These results obviously suggested that impairment on seminal antioxidants is an important risk factor for low sperm quality associated to idiopathic infertility and as a result can lead to poor IVF outcome.

  6. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.

    Science.gov (United States)

    Engler, Mary B; Engler, Marguerite M; Chen, Chung Y; Malloy, Mary J; Browne, Amanda; Chiu, Elisa Y; Kwak, Ho-Kyung; Milbury, Paul; Paul, Steven M; Blumberg, Jeffrey; Mietus-Snyder, Michele L

    2004-06-01

    Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. Cardioprotective effects including antioxidant properties, inhibition of platelet activity, and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids. To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects. The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz). High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.

  7. Activation of gastric afferents increases noradrenaline release in the paraventricular nucleus and plasma oxytocin level.

    Science.gov (United States)

    Ueta, Y; Kannan, H; Higuchi, T; Negoro, H; Yamaguchi, K; Yamashita, H

    2000-01-14

    Effects of electrical stimulation of the gastric vagal nerves on plasma levels of oxytocin (OXT) and arginine vasopressin (AVP) were examined in rats anesthetized with urethane. Electrical stimulation of the gastric vagal nerves increased the plasma levels of OXT, but not AVP. The concentrations of extracellular noradrenaline (NA) in the paraventricular nucleus (PVN) were measured by in vivo microdialysis in rats anesthetized with urethane. Electrical stimulation of the gastric vagal nerves evoked an increase followed by a slight decrease in the concentrations of NA. The responses of spontaneous firing magnocellular neurosecretory neurons in the PVN to both electrical stimulation of the gastric vagal nerves and intravenous (i.v.) administration of CCK-8 were examined. Most of the putative OXT-secreting cells recorded were excited by both electrical stimulation of gastric vagal nerves and i.v. administration of CCK-8. These results suggest that gastric vagal afferents activate the central noradrenergic system from the brainstem to the PVN and secretion of OXT.

  8. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  9. Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

    DEFF Research Database (Denmark)

    Isaksson, G L; Stubbe, J; Hansen, Per Lyngs;

    2014-01-01

    We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC = f(Na...... = f(NaI) is altered by β1 -adrenoceptor blockade (metoprolol) and surgical renal denervation (DNX)....

  10. Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Theilade, Simone; Eugen-Olsen, Jesper;

    2016-01-01

    Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin ang...

  11. SELECTIVE AND TIME-RELATED ACTIVATION OF THE CARDIAC RENIN-ANGIOTENSIN SYSTEM AFTER EXPERIMENTAL HEART-FAILURE - RELATION TO VENTRICULAR-FUNCTION AND MORPHOLOGY

    NARCIS (Netherlands)

    PINTO, YM; DESMET, BGJL; VANGILST, WH; MONNINK, S; DEGRAEFF, PA; WESSELING, H

    1993-01-01

    Objective: The cardiac renin-angiotensin system is activated in experimental heart failure, but it is unknown at what stage of heart failure it becomes activated, and whether activation is related to ventricular dysfunction and dilatation. Changes in activity of cardiac, renal, and plasma angiotensi

  12. Increases in plasma holotranscobalamin can be used to assess vitamin B-12 absorption in individuals with low plasma vitamin B-12.

    Science.gov (United States)

    Bhat, Dattatray S; Thuse, Nileema V; Lubree, Himangi G; Joglekar, Charudatta V; Naik, Sadanand S; Ramdas, Lalita V; Johnston, Carole; Refsum, Helga; Fall, Caroline H; Yajnik, Chittaranjan S

    2009-11-01

    Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 microg (n = 191) or 2 microg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of > or =15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was 10 micromol/L in children and >15 micromol/L in adults). In the 10 microg group, the plasma holo-TC concentration increased by 4.8-fold from (mean +/- SD) 9.3 +/- 7.0 pmol/L to 53.8 +/- 25.9 pmol/L and in the 2 microg group by 2.2-fold from 11.1 +/- 8.5 pmol/L to 35.7 +/- 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.

  13. Increases in Plasma Holotranscobalamin Can Be Used to Assess Vitamin B-12 Absorption in Individuals with Low Plasma Vitamin B-12123

    Science.gov (United States)

    Bhat, Dattatray S.; Thuse, Nileema V.; Lubree, Himangi G.; Joglekar, Charudatta V.; Naik, Sadanand S.; Ramdas, Lalita V.; Johnston, Carole; Refsum, Helga; Fall, Caroline H.; Yajnik, Chittaranjan S.

    2012-01-01

    Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Weather malabosrption of the vitamin contributes to this has not been investigated. A rise in plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 μg (n=191) or 2 μg (n=122) of cyanocobalamin at 6 h intervals. A rise in plasma holo-TC of ≥15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 was 10 μmol/L in children and >15 μmol/L in adults). In 10 μg group plasma holo-TC concentration increased by 4.8 -fold from (mean ± SD) 9.3 ± 7.0 pmol/L to 53.8 ± 25.9 pmol/L, and in 2 μg group by 2.2 -fold from 11.1 ± 8.5 pmol/L to 35.7 ± 19.3 pmol/L. Only 10% of participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status. PMID:19776185

  14. MAC-2BP is increased in plasma during nephrotic syndrome and is produced by PBMC

    DEFF Research Database (Denmark)

    Andersen, René Frydensbjerg; Kamperis, Konstantinos; Rittig, Søren

    of the study was to investigate the urinary presence of the renal water channel AQP2 and it´s correlation to urine production in children with NS. METHODS: A total of 20 (7 girls) children with NS were included with a mean age of 9.1±3.2 yrs. Urine samples were collected from the second morning void at debut......OBJECTIVES: Edema is a hallmark of nephrotic syndrome (NS) and has largely been attributed to sodium retention. Yet low plasma sodium is frequently observed in children with acute NS suggesting that a disturbance in renal water handling may coexist together with sodium retention. The aim......, patients exhibit an increased excretion of AQP2 in urine compared with remission and increased uAQP2 concentration correlated with reduced urine production. Further studies are needed to investigate if uAQP2 contributes to a positive free water balance in NS independently of sodium retention....

  15. Renin-angiotensin system in ventilator-induced diaphragmatic dysfunction: Potential protective role of Angiotensin (1-7).

    Science.gov (United States)

    Sigurta', Anna; Zambelli, Vanessa; Bellani, Giacomo

    2016-09-01

    Ventilator-induced diaphragmatic dysfunction is a feared complication of mechanical ventilation that adversely affects the outcome of intensive care patients. Human and animal studies demonstrate atrophy and ultrastructural alteration of diaphragmatic muscular fibers attributable to increased oxidative stress, depression of the anabolic pathway regulated by Insulin-like growing factor 1 and increased proteolysis. The renin-angiotensin system, through its main peptide Angiotensin II, plays a major role in skeletal muscle diseases, mainly increasing oxidative stress and inducing insulin resistance, atrophy and fibrosis. Conversely, its counter-regulatory peptide Angiotensin (1-7) has a protective role in these processes. Recent data on rodent models show that renin-angiotensin system is activated after mechanical ventilation and that infusion of Angiotensin II induces diaphragmatic skeletal muscle atrophy. Given: (A) common pathways shared by ventilator-induced diaphragmatic dysfunction and skeletal muscle pathology induced by renin-angiotensin system, (B) evidences of an involvement of renin-angiotensin system in diaphragm atrophy and dysfunction, we hypothesize that renin-angiotensin system plays an important role in ventilator-induced diaphragmatic dysfunction, while Angiotensin (1-7) can have a protective effect on this pathological process. The activation of renin-angiotensin system in ventilator-induced diaphragmatic dysfunction can be demonstrated by quantification of its main components in the diaphragm of ventilated humans or animals. The infusion of Angiotensin (1-7) in an established rodent model of ventilator-induced diaphragmatic dysfunction can be used to test its potential protective role, that can be further confirmed with the infusion of Angiotensin (1-7) antagonists like A-779. Verifying this hypothesis can help in understanding the processes involved in ventilator-induced diaphragmatic dysfunction pathophysiology and open new possibilities for its

  16. Involvement of chloride in renin secretion from isolated rat glomeruli

    DEFF Research Database (Denmark)

    Skøtt, O; Jensen, B L

    1992-01-01

    M) inhibited renin release reversibly. Substitution of Cl- with nitrate (101 mM) stimulated renin secretion. Substitution with iodide (15 or 101 mM) had no consistent effect. The stimulation induced by calcium-free solutions was high in May and low in September. In the absence of chloride, the response....... It is concluded that the renin secretory process has a demand for permeant anions. The stimulation caused by low external calcium involves at least two mechanisms: one is anion sensitive, powerful, varies with the season, and includes a recruitment phenomenon; another is anion insensitive and weak....

  17. Fish meal supplementation increases bovine plasma and luteal tissue omega-3 fatty acid composition.

    Science.gov (United States)

    White, N R; Burns, P D; Cheatham, R D; Romero, R M; Nozykowski, J P; Bruemmer, J E; Engle, T E

    2012-03-01

    The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.

  18. Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance.

    NARCIS (Netherlands)

    Veldman, B.A.J.; Vervoort, G.M.M.; Blom, H.J.; Smits, P.

    2005-01-01

    INTRODUCTION: Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function.

  19. Radioimmunoassay of haemoglobin F in K 562 cells following induction with renin substrate and erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Rosenloef, K.; Fyhrquist, F.; Hortling, L.; Groenhagen-Riska, C. (Helsinki Univ. (Finland). Minerva Inst. for Medical Research; Helsinki Univ. (Finland). 4th Dept. of Medicine)

    1985-06-01

    To test the hypothesis of renin substrate (RS: angiotensinogen) being a precursor of erythropoietin (EP), the capacity of RS and EP to induce Hb synthesis was compared in cultured human erythroid leukaemia cells of the K 562 line after prestimulation with haemin. For this purpose a radioimmunoassay for haemoglobin F (HbF) was developed. This assay was shown to be specific for HbF, reproducible, and sensitive for 0.1 ng of HbF. The cells were induced by RS and EP to increased HbF production. Cells stimulated with RS or EP showed increased benzidine staining. These data support the hypothesis that renin substrate is a likely precursor of erythropoietin.

  20. Control of renin secretion from rat juxtaglomerular cells by cAMP-specific phosphodiesterases

    DEFF Research Database (Denmark)

    Friis, Ulla G; Jensen, Boye L; Sethi, Shala

    2002-01-01

    trequinsin increased cellular cAMP content, enhanced forskolin-induced cAMP formation, and stimulated renin release from incubated and superfused JG cells. Trequinsin-mediated stimulation of renin release was inhibited by the permeable protein kinase A antagonist Rp-8-CPT-cAMPS. PDE4C was also expressed......, and the PDE4 inhibitor rolipram enhanced cellular cAMP content. Dialysis of single JG cells with cAMP in whole-cell patch-clamp experiments led to concentration-dependent, biphasic changes in cell membrane capacitance (C(m)) with a marked increase in C(m) at 1 micromol/L, no net change at 10 micromol...

  1. Severe hypoglycaemia during pregnancy in women with type 1 diabetes: possible role of renin-angiotensin system activity?

    DEFF Research Database (Denmark)

    Nielsen, L Ringholm; Pedersen-Bjergaard, U; Thorsteinsson, B;

    2009-01-01

    AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded...... preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early...

  2. Effect of increased testicular temperature on seminal plasma proteome of the ram.

    Science.gov (United States)

    Rocha, David R; Martins, Jorge André M; van Tilburg, Mauricio F; Oliveira, Rodrigo V; Moreno, Frederico B; Monteiro-Moreira, Ana Cristina O; Moreira, Renato A; Araújo, Airton A; Moura, Arlindo A

    2015-11-01

    The present study evaluated the effects of heat stress on the ram seminal plasma proteome. Six Morada Nova rams were scrotal insulated for 8 days. Scrotal circumference, sperm parameters, and seminal fluid proteins were evaluated before (Day 0) and twice during scrotal insulation (Days 4 and 8), and weekly until semen parameters returned to preinsulation values (normal). Seminal proteins were analyzed by two-dimensional SDS-PAGE and mass spectrometry. Scrotal circumference decreased from 30 ± 0.4 cm on Day 0 to 22.6 ± 0.6 cm on Day 36 (P Rams were azoospermic between Days 29 and 64, and sperm concentration came back to normal on Day 92. The number of spots/two-dimensional gel reduced from 256 ± 31 on Day 0 to 104 ± 14 on Day 29 (when rams were azoospermic) and then increased to 183 ± 9 on Day 113 (P rams, indicating alterations in both spermatogenesis and sperm maturation. Changes of seminal plasma proteome were coincidental with variations in semen parameters. Proteins affected by heat challenge are potentially involved in sperm protection, maturation, and fertilization.

  3. The plasma concentration of the B cell activating factor is increased in children with acute malaria.

    Science.gov (United States)

    Nduati, Eunice; Gwela, Agnes; Karanja, Henry; Mugyenyi, Cleopatra; Langhorne, Jean; Marsh, Kevin; Urban, Britta C

    2011-09-15

    Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF)