Influence of converting-enzyme inhibition on rat des-angiotensin I-angiotensinogen

1984 ◽  
Vol 246 (2) ◽  
pp. E129-E133 ◽  
Author(s):  
E. Clauser ◽  
J. Bouhnik ◽  
M. F. Gonzalez ◽  
P. Corvol ◽  
J. Menard

The effects of high plasma renin levels on plasma levels of both total immunoreactive angiotensinogen (direct radioimmunoassay) and intact angiotensinogen measured by angiotensin I released by renin (indirect assay) were studied in sodium-depleted rats both with and without captopril treatment and in adrenalectomized rats. The direct assay measures both intact angiotensinogen and des-angiotensin I-angiotensinogen, its residue cleaved by renin. The indirect assay measures only intact angiotensinogen. Neither sodium depletion, captopril treatment, nor adrenalectomy modified the circulating levels of total angiotensinogen. However these treatments produced a decrease in intact angiotensinogen that was in proportion to the elevation of renin levels. The difference between the two assays for angiotensin represents the level of des-angiotensin I-angiotensinogen and correlated satisfactorily with the plasma levels of renin. Identical correlations were observed in adrenalectomized rats and captopril-treated rats. We conclude that des-angiotensin I-angiotensinogen levels are an index of activation of the renin-angiotensin system dependent on the circulating level of renin.

1991 ◽  
Vol 69 (9) ◽  
pp. 1381-1384 ◽  
Author(s):  
Knud Poulsen ◽  
Arne Høj Nielsen ◽  
Arne Johannessen

In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues.Key words: angiotensinogen, inactive renin, renin.


1991 ◽  
Vol 260 (6) ◽  
pp. R1200-R1209 ◽  
Author(s):  
D. L. Mattson ◽  
H. Raff ◽  
R. J. Roman

This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.


1975 ◽  
Vol 228 (2) ◽  
pp. 369-375 ◽  
Author(s):  
JS Carvalho ◽  
R Shapiro ◽  
P Hopper ◽  
LB Page

Micromethods for measurement of plasma renin concentration (PRC) and plasma renin-substrate concentration (PSC) have been developed for rat plasma with radioimmunoassay of angiotensin I. An improved technique for aortic implantation of plastic cannulas was developed for use in experiments 1-2 wk in duration. The effects on components of renin system of anesthesia and tail cutting were studied. Arterial blood was sampled through cannulas without animal manipulation. PRC varied little in unanesthetized rats, was moderately and variably increased during pentobarbital anesthesia, and was markedly and consistently elevated during ether anesthesia. PSC was unchanged during anesthesia. PRC was increased in blood obtained by tail cutting within 1-2 min after cutting. With the use of the methods and techniques described here serial studies of the renin system in plasma of unanesthetized rats are shown to be feasible. A role for the sympathetic nervous system in the mediation of renin secretion by ether is proposed.


2009 ◽  
Vol 296 (2) ◽  
pp. E343-E350 ◽  
Author(s):  
Jason D. Fowler ◽  
Stacy B. Krueth ◽  
David A. Bernlohr ◽  
Stephen A. Katz

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.


2021 ◽  
Author(s):  
Kevin Burns ◽  
Matthew Cheng ◽  
Todd Lee ◽  
Allison McGeer ◽  
David Sweet ◽  
...  

Abstract SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infection may therefore induce changes in the renin-angiotensin system (RAS). To determine the effects of COVID-19 on plasma RAS components, we measured plasma ACE, ACE2, and angiotensins I, (1-7), and II in 46 adults with COVID-19 at hospital admission and on days 2, 4, 7 and 14, compared to 50 blood donors (controls). We compared survivors vs. non-survivors, males vs. females, ventilated vs. not ventilated, and angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor-exposed vs. not exposed. At admission, COVID-19 patients had higher plasma levels of ACE (p=0.012), ACE2 (p=0.001) and angiotensin-(1-7) (p<0.001) than controls. Plasma ACE and ACE2 remained elevated for 14 days in COVID-19 patients, while plasma angiotensin-(1-7) decreased after 7 days. In adjusted analyses, plasma ACE was higher in males vs. females (p=0.042), and plasma angiotensin I was significantly lower in ventilated vs. non-ventilated patients (p=0.001). In summary, plasma ACE and ACE2 are increased for at least 14 days in patients with COVID-19 infection. Angiotensin-(1-7) levels are also elevated, but decline after 7 days. The results indicate dysregulation of the RAS with COVID-19, with increased circulating ACE2 throughout the course of infection.Clinical Trial Registration: https://clinicaltrials.gov/ Unique Identifier: NCT04510623


1993 ◽  
Vol 4 (6) ◽  
pp. 1354-1361
Author(s):  
C T Harker ◽  
M P O'Donnell ◽  
B L Kasiske ◽  
W F Keane ◽  
S A Katz

Recently, the obese Zucker rat (OZR), an animal model of non-insulin-dependent (type II) diabetes, was shown to respond to converting enzyme inhibition with decreased albuminuria and a marked attenuation of glomerular injury. It was hypothesized that the OZR would possess low plasma renin values and an increased vascular responsiveness to angiotensin II, and therefore, the renin-angiotensin system (PRA, active renin, inactive renin, renal renin content, and plasma angiotensinogen) and vascular reactivity in OZR at 10 and 24 wk of age were investigated. PRA and renin concentration, inactive plasma renin, and renal renin content were all significantly (P < 0.05) reduced in OZR when compared with age-matched lean controls. The ratio of inactive to total renin was significantly increased in the OZR. OZR aortic ring vascular reactivity to KCl, norepinephrine, and angiotensin II was assessed. Despite essentially equal or increased contractile responses to KCl and norepinephrine at both 10 and 24 wk of age, the OZR was not more sensitive to angiotensin II and displayed a significantly reduced contractile response to angiotensin II at 24 wk of age, when compared with lean age-matched controls. It was concluded that the renal protective effect of converting enzyme inhibition in OZR, despite significantly reduced PRA and concentration, inactive plasma renin, and renal renin content, may not be due to a diabetes-induced increased vascular reactivity to angiotensin II.


1983 ◽  
Vol 244 (2) ◽  
pp. R249-R256 ◽  
Author(s):  
J. E. Robillard ◽  
D. N. Weismann ◽  
R. A. Gomez ◽  
N. A. Ayres ◽  
W. J. Lawton ◽  
...  

The renal and adrenal responses to a continuous infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril were studied in 27 chronically catheterized sheep fetuses (less than 120 days gestation, n = 15, and greater than 130 days gestation, n = 12; term being 145 days) and in 12 newborn lambs between 8 and 21 days of age. Total renal blood flow did not change during ACE inhibition. However, the renal vascular resistance decreased significantly in newborn lambs (-21.8 +/- 5.7%) and in fetuses greater than 130 days (-21.7 +/- 4.7%) but not in fetuses less than 120 days. A significant decrease in filtration fraction (-19.2 +/- 6.5%) was observed in newborn lambs. No changes in urinary kallikrein and prostaglandin excretion rate were observed during ACE inhibition in any group of animals. ACE inhibition produced similar declines in blood pressure in both groups of fetuses (-10.2 +/- 3% in fetuses less than 120 days and -9.5 +/- 4.6% in fetuses greater than 130 days) and in newborn lambs (-13.4 +/- 2.1%). The percent changes in plasma renin activity were similar in all groups of animals. However, a significant decline in plasma aldosterone concentration was observed only in newborn lambs (from 130 +/- 31 to 64 +/- 9 pg/ml). These results suggest that the renin-angiotensin system might have physiological significance during maturation, but that this role seems to be more important in near-term fetuses (greater than 130 days) and postnatally than early in gestation.


1971 ◽  
Vol 51 (1) ◽  
pp. 79-90 ◽  
Author(s):  
PAMELA A. SIMPSON ◽  
J. R. BLAIR-WEST

SUMMARY A renin—angiotensin system was shown to be present in several marsupial species in plasma and homogenates of the renal cortex. Species studied were: Eastern Grey kangaroo (Macropus giganteus), Red kangaroo (Megaleia rufa), common wombat (Vombatus hirsutus), pademelon (Thylogale billardierii), Bennett's wallaby (Wallabia rufogrisea frutica), a quokka (Setonix brachyurus) and a tiger cat (Dasyurus maculatus). Renin-substrate was found in the plasma of the Eastern Grey kangaroo, the Red kangaroo and the wombat. Renin was shown to be present in the plasma of all species by incubation alone or with heterologous marsupial renin-substrate. Plasma renin concentration and renal renin content were estimated by an established method using standard sheep renin-substrate. Plasma renin concentration was high, suggesting that marsupial renins have a high affinity for sheep substrate; renal renin estimates were low relative to eutherian species, suggesting that renal storage may be small. Plasma renin concentration and renal renin levels were proportionately related. Renin levels were consistently lowest in the wombat. Bilateral nephrectomy of an Eastern Grey kangaroo reduced plasma renin concentration to zero and increased renin-substrate concentration eightfold. The angiotensin-like incubation product from Eastern Grey kangaroo renin-substrate did not cross react with antibodies to [5-Ile]-angiotensin I, suggesting that the product has a different sequence of amino acids.


1979 ◽  
Vol 57 (s5) ◽  
pp. 157s-160s ◽  
Author(s):  
Th. Unger ◽  
R. W. Rockhold ◽  
K. Schaz ◽  
P. Vescei ◽  
G. Bönner ◽  
...  

1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.


Sign in / Sign up

Export Citation Format

Share Document