MEASUREMENT OF PLASMA RENIN-SUBSTRATE IN MAN

1973 ◽  
Vol 56 (2) ◽  
pp. 159A-171 ◽  
Author(s):  
MALCOLM TREE
Keyword(s):  
Angiotensin Ii ◽  
Substrate Concentration ◽  
Plasma Renin ◽  
Angiotensin I ◽  
Renin Substrate ◽  
Potential Sources ◽  
Sources Of Variation ◽  
Method Of Measurement ◽  
Inhibitor Solution

SUMMARY Values of plasma renin-substrate concentration in man vary widely according to the method of measurement used. Potential sources of variation have been tested and, as far as possible, excluded in the method described here. Blood was diluted rapidly in an angiotensinase-inhibitor solution containing EDTA and phenanthroline; plasma was separated by centrifugation and the renin-substrate in the specimen was hydrolysed by renin to angiotensin I which was identified as such by chromatography and radioimmunoassay. Angiotensin I was used as a standard to determine the amount of angiotensin formed on incubation. Use of angiotensin II for a standard, as in other methods, led to falsely low values of plasma renin-substrate concentration. Recovery of added substrate was 94%. Changes of plasma renin-substrate concentration in some physiological and pathological states are reported briefly.

ESTIMATION OF MARSUPIAL RENIN USING MARSUPIAL RENIN-SUBSTRATE

1972 ◽  
Vol 53 (1) ◽  
pp. 125-130 ◽  
Author(s):  
PAMELA A. SIMPSON ◽  
J. R. BLAIR-WEST
Keyword(s):  
Substrate Concentration ◽  
Structural Difference ◽  
Plasma Renin ◽  
Angiotensin I ◽  
Ph Optimum ◽  
Ph Profile ◽  
Renin Substrate ◽  
Grey Kangaroo ◽  
Rate Of Reaction ◽  
Highly Correlated

SUMMARY Bilateral nephrectomy of an Eastern Grey kangaroo (Macropus giganteus) increased plasma renin-substrate concentration approximately tenfold when compared with intact kangaroos. A preparation made from this plasma had a renin-substrate concentration of 3000 ng/ml. A pH profile of rate of reaction with pig renin had an optimum at pH 5·39. By comparison, the pH optimum of sheep renin-substrate was pH 6·15. Estimates of plasma renin concentration for kangaroos, wombats and wallabies, using kangaroo renin-substrate or sheep renin-substrate were highly correlated. Results from incubation with sheep renin-substrate were greater and hence indicate the advantage in using this substrate for marsupial renin estimation. The consistently large difference between sheep and kangaroo renin-substrate when incubated with renin from marsupial and eutherian species appears to be due to a structural difference between the two substrates, probably near the C-terminal end of the angiotensin I molecule.

scholarly journals Effects of angiotensin II,thyroxine and estrogen on plasma renin substrate concentration and renin substrate production by the liver.

1981 ◽  
Vol 45 (9) ◽  
pp. 1078-1082 ◽  
Author(s):  
EIKI MURAKAMI ◽  
KUNIO HIWADA ◽  
TATSUO KOKUBU
Keyword(s):  
Angiotensin Ii ◽  
Substrate Concentration ◽  
Plasma Renin ◽  
Renin Substrate

Intrarenal Formation of Angiotensin II in the Rat: Interference by Saralasin and SQ 20881

1974 ◽  
Vol 48 (s2) ◽  
pp. 37s-40s
Author(s):  
H. Zschiedrich ◽  
K. G. Hofbauer ◽  
E. Hackenthal ◽  
G. D. Baron ◽  
F. Gross
Keyword(s):  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Plasma Renin ◽  
Rat Plasma ◽  
Renal Vascular Resistance ◽  
Angiotensin I ◽  
Renin Substrate ◽  
Vasoconstrictor Effect ◽  
Renal Vascular ◽  
Dose Dependent

1. Isolated rat kidneys were perfused with a medium free of components of the renin-angiotensin system. 2. Angiotensin II, angiotensin I, tetradecapeptide renin substrate or rat plasma renin substrate added to the medium caused a dose-dependent increase of renal vascular resistance. 3. The vasoconstrictor effect of angiotensin II was inhibited by 1-Sar-8-Ala-angiotensin II (Saralasin). The inhibition was dose-dependent, being complete at the highest doses applied. In this dose range, Saralasin increased renal vascular resistance. Saralasin also inhibited vasoconstriction induced by tetradecapeptide renin substrate. 4. The vasoconstrictor effect of angiotensin I was suppressed by SQ 20881, up to a maximum of 87% depending on the dose. Similarly the increase in renal vascular resistance induced by a purified preparation of rat plasma renin substrate was inhibited by 55%; no effect on the action of tetradecapeptide renin substrate was observed. 5. The data suggest that, within the kidney, angiotensin I is converted into angiotensin II to the extent of about 1.25%. Since no angiotensin I is formed from synthetic renin substrate, the vasoconstrictor effect of the tetradecapeptide may be either due to a direct interaction with the angiotensin II receptor or the consequence of the intrarenal formation of angiotensin II. In contrast, the results with rat plasma renin substrate suggest that angiotensin I is formed from ‘natural’ substrate and is subsequently converted into angiotensin II.

Captopril Combined with Thiazide Lowers Renin Substrate Concentration: Implications for Methodology in Renin Assays

1981 ◽  
Vol 60 (5) ◽  
pp. 591-593 ◽  
Author(s):  
S. Rasmussen ◽  
M. Damkjaer Nielsen ◽  
J. Giese
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Substrate Concentration ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Renin Substrate ◽  
Activity Measurements ◽  
Captopril Treatment

1. We have measured plasma concentrations of renin, renin substrate and angiotensins I and II as well as plasma renin activity in nine patients with severe or malignant hypertension during treatment with captopril, hydrochlorothiazide and propranolol. 2. On captopril and hydrochlorothiazide the plasma concentrations of renin substrate and angiotensin II decreased markedly, while renin and angiotensin I levels were increased. 3. The changes in renin substrate concentration suggest a consumption of substrate induced by an increased renin release. Further, the positive feedback of angiotensin II on hepatic renin substrate synthesis may be inhibited. 4. The sequential changes in renin release during captopril treatment should be monitored by measuring plasma renin concentration since plasma renin activity measurements will be profoundly influenced by the marked changes in plasma renin substrate concentration.

Increase of Plasma Renin-Substrate Concentration after Infusion of Angiotensin in the Rat

1973 ◽  
Vol 44 (1) ◽  
pp. 87-90 ◽  
Author(s):  
M. Khayyall ◽  
J. MacGregor ◽  
J. J. Brown ◽  
A. F. Lever ◽  
J. I. S. Robertson
Keyword(s):  
Angiotensin Ii ◽  
Plasma Protein ◽  
Substrate Concentration ◽  
Protein Concentration ◽  
Plasma Renin ◽  
Plasma Protein Concentration ◽  
Renin Substrate

1. Compared with sixteen control animals infused with saline, plasma renin-substrate concentration increased twofold (P < 0.001) in twenty-two rats following infusion of angiotensin II at a mean rate of 191 ng kg−1 min−1 for 13 h. 2. The change was not attributable to an overall increase of plasma protein concentration.

Measurement of inactive renin in normal, nephrectomized, and adrenalectomized rats

1991 ◽  
Vol 69 (9) ◽  
pp. 1381-1384 ◽  
Author(s):  
Knud Poulsen ◽  
Arne Høj Nielsen ◽  
Arne Johannessen
Keyword(s):  
Animal Model ◽  
Exchange Resin ◽  
Cation Exchange Resin ◽  
Plasma Renin ◽  
Rat Plasma ◽  
Angiotensin I ◽  
Renin Substrate ◽  
Suitable Animal Model ◽  
Inactive Renin ◽  
Adrenalectomized Rats

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.

Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

1984 ◽  
Vol 62 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Ernesto L. Schiffrin ◽  
Jolanta Gutkowska ◽  
Gaétan Thibault ◽  
Jacques Genest
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Ace Inhibition ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

Intrarenal renin inhibition increases renal function by an angiotensin II-dependent mechanism

1988 ◽  
Vol 255 (4) ◽  
pp. F749-F754 ◽  
Author(s):  
H. M. Siragy ◽  
N. E. Lamb ◽  
C. E. Rose ◽  
M. J. Peach ◽  
R. M. Carey
Keyword(s):  
Renal Function ◽  
Angiotensin Ii ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Competitive Inhibitor ◽  
Urinary Flow ◽  
Renin Substrate ◽  
Plasma Aldosterone Concentration ◽  
Renin Inhibition

ACRIP is a competitive inhibitor of renin in which an analogue of statine, (3R,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of porcine renin substrate. ACRIP inhibits the enzymatic activity of renin, thus blocking the initiation of the angiotensin cascade. We studied the intrarenal action of ACRIP in small quantities without measurable systemic effects on renal function. In the first experiment, ACRIP was administered intrarenally at 0.02, 0.2, and 2 micrograms.kg-1.min-1 to uninephrectomized conscious dogs (n = 6) in metabolic balance at sodium intake of 10 meq/day. ACRIP, in doses of 0.02 and 0.2 micrograms.kg-1.min-1, markedly increased urine sodium excretion (UNaV) from 5.8 +/- 1.4 to 15.1 +/- 5.1 and 19.9 +/- 3.2 mu eq/min, respectively. Urinary flow rate (UV) underwent a similar increase and glomerular filtration rate (GFR) increased from 25.7 +/- 2.5 to 35.6 +/- 2.5 at 0.02 micrograms.kg-1.min-1 of ACRIP. Renal plasma flow (RPF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were not affected. At 2 micrograms.kg-1.min-1, ACRIP traversed the kidney in quantities large enough to produce a reduction in systemic PRA and mean arterial pressure and caused natriuresis, diuresis, and increased GFR. In a second experiment, ACRIP was administered intrarenally at 0.2 micrograms.kg-1.min-1 in a separate group (n = 4) under identical conditions. ACRIP-induced increases in UV and UNaV were completely blocked by concurrent intrarenal administration of angiotensin II. The results indicate that intrarenal angiotensin II acts as a physiological regulator of renal sodium and fluid homeostasis.

Renin, Angiotensin and Aldosterone in Human Pregnancy and the Menstrual Cycle

1971 ◽  
Vol 16 (3) ◽  
pp. 183-196 ◽  
Author(s):  
J. I. S. Robertson ◽  
R. J. Weir ◽  
G. O. Düsterdieck ◽  
R. Fraser ◽  
M. Tree
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin ◽  
Normal Pregnancy ◽  
Maternal Plasma ◽  
Plasma Aldosterone ◽  
Sodium Depletion ◽  
Aldosterone Secretion ◽  
Renin Substrate ◽  
Plasma Aldosterone Concentration ◽  
In Pregnancy

Aldosterone secretion is frequently, although not invariably, increased above the normal non-pregnant range in normal pregnancy. Substantial increases in plasma aldosterone concentration have also been demonstrated as early as the sixteenth week. In pregnancy, aldosterone secretion rate responds in the usual way to changes in sodium intake. Plasma renin concentration is frequently, but not invariably, raised above the normal non-pregnant range. Plasma renin-substrate is consistently raised in pregnancy. Plasma angiotensin II has also been shown usually to be raised in a series of pregnant women. A significant positive correlation has been shown between the maternal plasma aldosterone concentration and the product of the concurrent plasma renin and renin-substrate concentrations. This suggests that the increased plasma aldosterone in pregnancy is the consequence of an increase in circulating angiotensin II, which in turn is related to the level of both renin and its substrate in maternal blood. For these reasons, estimations of renin activity in pregnancy are of dubious value. The increased renin, angiotensin and aldosterone concentrations may represent a tendency to maternal sodium depletion, probably mainly a consequence of the increased glomerular filtration rate. It is possible that the nausea and other symptoms of early pregnancy may be a consequence of this tendency to sodium depletion, with its attendant hormonal changes. In ‘pre-eclampsia’, renin and aldosterone values are generally slightly lower than in normal pregnancy. Human chorion can apparently synthesize renin independently of the kidney. The physiological significance of this remains at present obscure, but it seems unlikely that this source contributes much, if at all, to the often elevated maternal plasma renin. Plasma renin, renin-activity and angiotensin II concentrations, and aldosterone secretion are increased in the luteal phase of the menstrual cycle.

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