Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RENIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1979

Measurement of plasma renin concentration using exogenous human renin substrate in normal subjects: correlation with plasma renin concentration and plasma aldosterone concentration.

Measurement of plasma renin concentration (PRC) was done in normal subjects at rest and under acute stimulation of renin release under unrestricted sodium intake. Concurrent measurements of plasma renin activity (PRA) and plasma aldosterone concentration (PA) were carried out. The mean values of PRC at rest and after stimulation of renin release were 12.8 +/- 1.3 (SEM) and 21.7 +/- 4.4 (SEM) ng AT I/ml/h, respectively. These corresponded to renin contents of 3.4 +/- 0.34 (SEM) X 10(-5) Goldblatt units and 5.8 +/- 0.36 (SEM) respectively. The mean percent increase of PRC (82.1 +/- 19.3 (SEM)) %) was almost indentical to that of PA (81.5 +/- 16.4 (SEM) %), but differed from that of PRA (269 +/- 83.1 (SEM) %). A very high correlation between concurrent PRC and PA (r = 0.92, P less than 0.001) was found in normal subjects at rest and under acute stimulation of renin release. A good correlation between PRC and PRA (r = 0.85, P less than 0.001) was also observed. However, a higher correlation between percent increases of PRC and PA (r = 0.92, P less than 0.001) than that of PRA and PA (r = 0.80, 0.01 less than P less than 0.005) was found. Results show that PRA is a good index of the renin content in plasma in normal subjects at rest and PRC reflects actual renin concentration in plasma at rest as well as under stimulation of renin release.

Adult↗
PubMed1986

Effect of age on the renin-angiotensin-aldosterone system in normal subjects: simultaneous measurement of active and inactive renin, renin substrate, and aldosterone in plasma.

To investigate the effect of aging on the renin-angiotensin-aldosterone system, plasma renin substrate concentrations (PRSC); plasma total, active, and inactive renin concentrations (TRC, ARC, and IRC); PRA; and plasma aldosterone concentrations (PAC) were measured simultaneously in 60 normal subjects, 18-84 yr old. PRSC was measured by the addition of excess human renal renin. ARC and TRC after trypsin activation were measured by adding sheep renin substrate; IRC was calculated by subtracting ARC from TRC. The active renin ratio was calculated as follows: ARC/TRC X 100%. PRA and PAC were measured by RIA. There were no significant changes in PRSC, TRC, IRC, and PRA to PAC ratio with aging. Both ARC and active renin ratio fell significantly with aging (r = 0.46 and P less than 0.01; and r = 0.54 and P less than 0.01, respectively). PRA and PAC also tended to decrease with aging (r = 0.35 and P less than 0.01; and r = 0.59 and P less than 0.01, respectively). A significant positive correlation was found between PRA and ARC (r = 0.72; P less than 0.001). PRA was also correlated with PAC. In conclusion, the age-related decrease in PRA is not due to the change in PRSC, but is mainly due to the fall in ARC. Decreased conversion of inactive to active renin might be responsible in part for the reduced ARC in the elderly.

Adolescent↗
PubMed2000

Normal blood pressure and plasma renin activity in mice lacking the renin-binding protein, a cellular renin inhibitor.

In renal extracts, some renin is present as "high molecular weight renin," a heterodimeric complex of renin with the 46-kDa renin-binding protein (RnBP), also known as N-acyl-D-glucosamine 2-epimerase. Because RnBP specifically inhibits renin activity, the protein was proposed to play an important role in the regulation of the renin-angiotensin system (RAS). Using gene targeting, we have generated mice lacking RnBP and tested this hypothesis in vivo. In particular, we analyzed biosynthesis, secretion, and activity of renin and other components of the RAS in mice lacking RnBP. Despite extensive investigations, we were unable to detect any major effects of RnBP deficiency on the plasma and renal RAS or on blood pressure regulation. Contrary to previous hypotheses, we conclude that RnBP does not play a significant role in the regulation of renin activity in plasma or kidney. However, RnBP knockout mice excrete an abnormal pattern of carbohydrates in the urine, indicating a role of the protein in renal carbohydrate metabolism.

Animals↗
PubMed2000

Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.

Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI). Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen-deficient mice. We recently found the decreased density in granular layer cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.

Angiotensin I↗
PubMed1979

Maternal and fetal renin activity and renin and big renin concentrations in second-trimester pregnancy.

Plasma renin activity (PRA) and the concentrations of renin (PRC) and big renin (PBRC) have been determined in maternal and fetal blood, and renin and big renin have been measured in amniotic fluid, at 16 to 20 weeks of gestation. Gradients between peripheral arterial and venous and uterine venous maternal circulation were not apparent for PRA, PRC, or PBRC. PRC and PBRC but not PRA were consistently higher in fetal cord blood than in the maternal compartment. The concentrations of big renin and of renin were tenfold higher in amniotic fluid than in maternal plasma and were significantly correlated in amniotic fluid but not maternal or fetal plasma.

Amniotic Fluid↗
PubMed1976

Contrasting effects of hypoglycemia on plasma renin activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) in low renin and normal renin essential hypertension.

Insulin-induced hypoglycemia previously has been shown to provoke a beta-adrenergic response that normally results in an increase in plasma renin activity (PRA). In our study, hypoglycemia induced definite increases in PRA in a group of five patients with normal renin essential hypertension but failed to do so in a group of six patients with low renin essential hypertension. In both groups, plasma cyclic adenosine 3',5'-monophosphate (cyclic AMP; cAMP) increased more than 2-fold during hypoglycemia, but the response in the low renin group was significantly less than that previously observed in normal subjects under the same conditions. Plasma cortisol increased to an equal extent in both groups of hypertensive patients during hypoglycemia. Infusion of the phosphodiesterase inhibitor, theophylline, resulted in definite increases of PRA in patients with normal renin hypertension but not in patients with low renin hypertension. Because changes in the level of plasma cAMP during hypoglycemia have been thought to reflect adrenal catecholamine release, our finding of a blunted increase in plasma cAMP during hypoglycemia in patients with low renin hypertension may suggest that there is a generalized alteration in adrenergic responsiveness in this condition.

Adrenal Medulla↗
PubMed1982

Molecular characterization of inactive renin: complete purification of prorenin in hog kidney and isolation of inactive renin from neuroblastoma cells: evidence for 2 different types of inactive renin.

To determine the molecular properties of inactive renin and its relationship to active renin, inactive renin in hog kidney was purified by devising affinity chromatography. Electrophoretically homogeneous inactive renin was prepared by 3 million-fold purification. It consists of a single polypeptide chain and undergoes reduction in molecular weight from 50,000 to 38,000 upon activation by proteases but not by dissociative treatment. This type of inactive renin is considered as a zymogen. However, a stable complex of renin and its inhibitor with a molecular weight of 110,000 was found in cultured neuroblastoma cells indicating the presence of a second type of inactive renin.

Animals↗
PubMed1991

Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an active renin inhibitory peptide template and their evaluation in a human renin infused rat model and in conscious sodium-depleted monkeys.

We previously reported that Boc-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]-Ile-Amp (1) is a potent and specific inhibitor of human renin in vitro. It was shown to resist degradation by selected proteases and a rat liver homogenate. It was shown to inhibit plasma renin activity and to reduce blood pressure in renin-dependent-animal models both by the intravenous and by the oral routes using dilute citric acid as vehicle. In an effort to discover compounds with improved pharmacological efficacy, we set out to modify the physical characteristics of this highly lipophilic renin inhibitor by incorporation of hydrophilic end groups. We report here a variety of water-solubilizing groups and the resulting structure-activity relationship of these compounds. They all maintain an extremely high level of enzyme inhibitory activity in vitro. Evaluation of these potent renin inhibitors in a human renin infused rat model suggests that some of these compounds exhibit improved pharmacological efficacy in vivo. This observation was further confirmed in the conscious sodium-depleted cynomolgus monkey. Importantly, the oral efficacy was demonstrated in a water vehicle in the absence of citric acid.

Animals↗
PubMed1980

Identification of renin and renin-like enzymes in rat brain by a renin-specific antibody.

1. The major angiotensin I-generating activity of rat brain extracts has a pH optimum different from that of renal renin and is not inhibited by renin specific antibody. 2. Affinity chromatography utilizing renin specific antibody, pepstatin and alpha-casein yielded fractions that resembled renal renin more closely with respect to antibody inhibition and pH optimum as well as an absence of the ability to hydrolyse haemoglobin. 3. We conclude that rat brain contains a host of enzymes with angiotensin I-generating activity including acid and neutral proteases and an enzyme with the immunochemical identity of renal renin. The biosynthetic origins of this renin-like protein remain uncertain.

Angiotensin I↗
PubMed1990

Circadian variations of total renin, active renin, plasma renin activity and plasma aldosterone in clinically healthy young subjects.

The direct assay of total renin (TRC) and active renin concentration (ARC) is a reality due to the availability of monoclonal antibodies against human renin. Because of this, a study has been performed in order to assess the circadian rhythmicity of TRC and ARC. The study was extended to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) for a more complete assessment of the renin-angiotensin-aldosterone system (RAAS). Twelve clinically healthy subjects (6 males and 6 females, age from 20 to 25 years) volunteered for this study. Time-qualified data series were analysed by means of chronobiological procedures in order to validate the circadian rhythm and to correlate the sinusoidal profiles. The circadian rhythm was validated at a high significance for TRC, ARC, PRA and at a borderline significance for PAC. The periodic oscillations were significantly correlated, demonstrating that TRC, ARC, PRA and PAC cycles oscillate in synchronism during the 24-hour span.

Adult↗
PubMed1984

Renin cleavage of a human kidney renin substrate analogous to human angiotensinogen, H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-OH, that is human renin specific and is resistant to cathepsin D.

A synthetic tetradecapeptide, H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Ser-OH, which corresponds to the 13 amino terminal residues of human angiotensinogen plus a carboxy terminal serine to replace a suggested site of carbohydrate attachment, has been shown to be a good substrate for human kidney renin. At pH 7.2 and 37 degrees C the KM or Michaelis constant was 8.4 +/- 2.9 microM, and the VM or velocity at infinite tetradecapeptide concentration was 11.3 +/- 2.4 mumol angiotensin I made per hour per milligram renin. The tetradecapeptide was highly resistant to cleavage by mouse submaxillary renin. The tetradecapeptide was also slowly cleaved by human liver cathepsin D, by rabbit lung angiotensin-converting enzyme, and by reconstituted human serum, but did not yield angiotensin I. Thus, this synthetic renin substrate should permit more specific measurement of human kidney renin activity.

Amino Acid Sequence↗
PubMed2004

Active renin versus plasma renin activity to define aldosterone-to-renin ratio for primary aldosteronism.

BACKGROUND: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become an established screening method for the diagnosis of primary aldosteronism. Plasma renin activity (PRA) is usually measured to define ARR although, increasingly, renin concentration alone is often measured in clinical routine. OBJECTIVE: To determine the threshold of ARR using active renin concentration to screen for primary aldosteronism. DESIGN AND PARTICIPANTS: To determine the ARR threshold based on plasma immunoreactive renin concentration (irR), we measured plasma aldosterone concentration (PAC), irR and PRA in 36 hypertensive patients, nine thereof with adrenal adenoma, and compared ARRs calculated from irR and PRA, respectively. SETTING: Single-centre, hypertension clinic in a tertiary care hospital. RESULTS: PRA ranged from 0.41-14.9 ng/ml per h and irR from 1.1-72 ng/l. There was an excellent correlation between PRA and irR (r = 0.98, P < 0.0001) and between ARRPRA and ARRirR (r = 0.96, P < 0.0001). An ARRPRA > 750 pmol/l per ng/ml per h was previously found to be highly predictive of primary aldosteronism because 90% of the corresponding patients failed to suppress PAC upon saline infusion or fludrocortisone. The corresponding threshold value for ARRirR was 150 pmol/ng in our patients. Using these cut-offs, nine subjects had both increased ARRPRA and ARRirR while, in three patients, either ARRPRA or ARRirR were increased. The nine patients with increased ARRPRA and ARRirR also had PAC > 650 pmol/l. Only these patients had adrenal adenomas. CONCLUSIONS: The ARR threshold to screen for primary aldosteronism may be based on measurement of irR. An ARRirR > 150 pmol/ng may indicate primary aldosteronism.

Adenoma↗
PubMed1984

The influence of plasma renin substrate on the relationship between plasma renin activity and plasma renin concentration. An experimental study in hyper- and hypothyroid rats.

The effects of endogenous Plasma Renin Substrate (PRS) on the relationship between Plasma Renin Activity (PRA) and the Plasma Renin Concentration (PRC) have been studied in hyperthyroid rats, by I-triiodothyronine (T3) administration and in hypothyroid rats, by propylthiouracil (PTU) treatment, to clarify if PRA changes are an adequate index for evaluating the renin-angiotensin changes during the alterations in the thyroid function. Although in experimental situations studied the induced variation on PRC explains a 62 per cent of the changes in PRA, finding a good lineal correlation between both parameters (r = 0.79, P less than 0.001). Not only does PRS play an important role on the kinetic of the enzymatic reaction but also explains jointly with PRC up to a 85 per cent of PRA alterations. PRS changes become more important during thyrotoxicosis where they limit in a higher degree the velocity of reaction due to inverse relationship between PRC and PRS (r = 0.74, P less than 0.001).

Angiotensinogen↗
PubMed2005

Renin release in response to Renin system blockade: activation of the Renin system in type 1 diabetes mellitus.

Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade. Forty-four consecutively enrolled Type 1 diabetic patients (28.2+/-1.5 years) and 37 normal subjects (37+/-2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan. As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6+/-1 ng/mL Ang I/hour in diabetic patients, and 1.7+/-0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1+/-17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2+/-13.9 ml/minute/1.73 m2; p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.

Adult↗
PubMed1998

[Assessment of active renin instead of plasma renin activity in the renin captopril test].

In the study usefulness of active renin (AR) measurement instead of plasma renin activity (PRA) in the diagnosis of reno-vascular hypertension(RVH) was evaluated. 42 patients with arterial hypertension (17F, 25M; mean age 45 + 12 years) and suspicion on RVH on the ground of the abnormal result of the preliminary renal angioscintigraphy were qualified to the study. Angioscintigraphic (SCT) and simultaneously renin captopril test (RCT) followed by renal arteriography or Doppler ultrasonography of renal arteries were performed in every case Haemodynamic significant stenosis of renal artery was revealed in 5 cases. The results of the examination in this group were as follows: in 3 patients positive RCT with PRA, in 4 patients positive RCT with R and in 2 patients positive SCT were found. The false positive results of RCT using PRA were obtained in 5 patients and only in 2 patients if using AR. There were no false positive results of SCT. The introduction of AR instead of PRA in RCT resulted in simplification and shortening of the diagnostic procedure. Furthermore, this modification increased detection of hemodynamically significant stenosis of renal artery from 2 cases revealed with SCT and 3 cases with PRAin RCT to 4 cases with AR. The successful preliminary results let us to introduce this modification of RCT to routine out-patients screening for RVH.

Adult↗
PubMed1995

Effect of acute and chronic losartan therapy on active and inactive renin and active renin glycoforms.

Plasma active renin consists of multiple glycoforms, which are differentially stored and secreted by the kidney, have varying plasma half-lives, and appear to have differing effects on renal sodium and water metabolism. Acute stimulation of renal renin secretion results in a disproportionate increase in plasma concentrations of the less negatively charged renin glycoforms and a decrease in the plasma half-life of active renin. The effects of chronic stimulation have not been well studied. We studied the effect of acute and chronic (42 days) stimulation of the renin angiotensin system with the AT1 selective angiotensin II receptor antagonist losartan on plasma active renin, active renin glycoforms separated by isoelectric focusing, and inactive renin in 11 essential hypertensive patients. A single 50 mg dose of losartan significantly increased plasma active renin concentration (ARC) from a pretreatment baseline of 3.2 +/- 1.1 to 7.2 +/- 2.3 ng AI/mL/h, 4 h postdose. This was primarily due to an increase in plasma concentrations of the less negatively charged active renin forms. After 42 days of losartan monotherapy, plasma ARC at losartan trough had increased significantly to 7.8 +/- 3.1 ng AI/mL/h, although the proportions of active renin forms were identical to baseline. Plasma ARC also increased significantly from 7.8 +/- 3.1 to 14.9 +/- 6.0 ng AI/mL/h acutely after the losartan dose on day 42 primarily due to increased plasma concentrations of less negatively charged active renin forms. Although plasma inactive renin concentrations did not change acutely after losartan dosing on day 1 or 42 they did increase from 27.3 +/- 7.8 before losartan day 1 to 37.0 +/- 13.7 ng AI/mL/h (P = .14) before losartan day 42. Thus, both acute and acute on chronic stimulation of renal renin secretion increased circulating ARC and shifted the profile of circulating renin toward the less negatively charged forms but did not change inactive renin concentrations. Chronic stimulation of renal renin secretion with losartan increased plasma concentrations of both active and inactive renin, but did not alter the proportions of active renin forms. Since the less negatively charged active renin forms have relatively short plasma half-lives, acute, but not chronic renal renin secretion is associated with a change in plasma renin half-life. Chronic stimulation of renal renin secretion with losartan presumably increased renin gene expression and resulted in increased constitutive secretion of inactive renin, increased constitutive secretion of negatively charged active renin forms, and increased renal storage of less negatively charged renin forms that were then available for acute regulated release.

Antihypertensive Agents↗
PubMed1984

Renin biosynthesis by human tumoral juxtaglomerular cells. Evidences for a renin precursor.

Renin biosynthesis was studied in a juxtaglomerular cell tumor. The tumoral tissue had a high renin content (180 Goldblatt Units/g of tissue), was heavily stained by immunofluorescence using human renin antiserum, and exhibited numerous characteristic secretory granules by electron microscopy. In one series of experiments, renin biosynthesis was studied in tissue slices, by following the incorporation of radiolabeled amino acids into specific immunoprecipitable renin. Time course studies showed that renin was first synthesized in a high molecular weight form, 55,000 mol wt, i.e., 10,000 mol wt higher than that of active renin, and was then converted into a 44,000-mol wt form. In a second series of experiments renin tumoral cells were cultured. Small, round, birefringent cells obtained after collagenase digestion produced renin in both primary culture and subculture media. After 5 d most of the renin found in the culture medium was inactive, but could be activated by trypsin treatment. The tumoral tissue exhibited a strong renin immunofluorescence and numerous secretory granules were observed by electron microscopy. In contrast, the renin-producing cells isolated from this tumor and grown in culture showed little renin immunofluorescence and no secretory granule could be observed. The renin-producing cells in primary culture and subculture were pulsed with radiolabeled amino acids, and immunoprecipitable radiolabeled renin was found in the culture media, thus demonstrating the actual biosynthesis of the enzyme. This renin was not stored inside cultured cells but was rapidly released into the medium and had a molecular weight of 55,000. No conversion of this inactive high molecular weight renin into the active, 44,000 mol wt form of renin was observed. We postulate the existence of two pathways for the processing, packaging, and secretion of renin in the tumoral cells: in juxtaglomerular cells of tumoral tissue renin is synthesized as a preprorenin and rapidly converted into prorenin (55,000 mol wt), which is in turn packaged in secretory granules where it is processed into active renin (44,000 mol wt) and finally secreted; in the cultured tumoral cells renin is still biosynthesized as a preprorenin molecule and then converted into prorenin, but is neither stored as granules nor processed into active renin. In this case the renin is released in an inactive form.

Adult↗