Effects of frusemide and captopril on the relationship between biologically and immunologically active renin in human plasma

1988 ◽  
Vol 75 (6) ◽  
pp. 669-672 ◽  
Author(s):  
Jitsuo Higaki ◽  
Toshio Ogihara ◽  
Yuichi Kumahara

1. The plasma renin concentration (PRC) and active renin concentration determined by radioimmunometric assay (ARC) were measured before and after administration of frusemide or captopril to normal volunteers. 2. Injection of 40 mg of frusemide followed by 1 h in the upright position significantly increased both PRC (P < 0.001) and ARC (P < 0.001). Oral administration of 50 mg of captopril also increased PRC (P < 0.05) and ARC (P < 0.05). 3. ARC and PRC were linearly correlated in the basal supine position [y = 0.635 x − 0.048 (y = PRC, x = ARC), r = 0.958, P < 0.001], after frusemide injection and standing (y = 0.800x + 0.359, r = 0.793,P < 0.02) and after captopril administration in the supine position (y = 0.938x − 0.555, r = 0.998,P < 0.001). 4. A cross-calibration study in which pure human renin was added to pooled plasma and PRC and ARC were measured showed linearity between the values obtained by the two methods. 5. The regression line for values of PRC and ARC in the supine position after captopril administration had a significantly greater slope (P < 0.001) and that for values after frusemide injection and standing was significantly elevated (P < 0.001) compared with the regression line for basal values in the supine position. 6. These results show that the biological activity of renin may be increased by various acute stimulations of renin to inappropriately high levels compared with the immunological activity. This implies that the mode of processing of human plasma renin may be altered by acute stimulation of renin. Furthermore, current methods for assay of plasma active renin may give erroneous values in various pathophysiological conditions.

1996 ◽  
Vol 271 (1) ◽  
pp. H184-H191
Author(s):  
S. A. Katz ◽  
J. A. Opsahl ◽  
L. M. Forbis ◽  
W. Ayenew

Active renin and five major active renin glycoforms were measured in plasma and the carotid wall of anesthetized rabbits before and after 1.5- and 24-h bilateral nephrectomy (BNX). Before BNX, there was no difference in renin glycoform proportions between plasma and the carotid wall. Plasma renin concentration (PRC) fell by 67% after 1.5-h BNX due to preferential clearance of renin glycoforms I+II, but no significant change in renin concentration was seen in the carotid artery (or aorta). Twenty-four hours after BNX, PRC and carotid wall renin concentrations were reduced by 99.7 and 97.7%, respectively, while the proportion of renin glycoforms I+II in the carotid wall was significantly elevated. These data are consistent with the view that vascular renin is derived from plasma renin of renal origin. After BNX, renin disappearance from the carotid (and aortic wall) is slower than renin decay from plasma, and the less negatively charged active renin glycoforms I+II exit the carotid wall much more slowly than the more negatively charged glycoforms. After 24-h BNX, renin glycoforms I+II were still effluxing from the vascular wall and represented the only glycoforms present in the carotid wall.


1992 ◽  
Vol 38 (10) ◽  
pp. 1959-1962 ◽  
Author(s):  
D Simon ◽  
D J Hartmann ◽  
G Badouaille ◽  
G Caillot ◽  
T T Guyenne ◽  
...  

Abstract A sensitive immunoradiometric assay, without an enzymatic step and specific for active human renin, was developed with use of two monoclonal antibodies (MAbs). In this assay system, the first MAb was coupled to magnetic beads (Magnogel); the second one, directed against the active form of the enzyme, was radiolabeled with 125I. The specificity of this assay was demonstrated in experiments measuring the active plasma renin concentration in the presence or absence of inactive renin. The assay, performed in two steps, was sensitive enough to detect 0.9 pg of renin per tube (3.5 ng/L). Intra- or interassay CVs were &lt; 10%. Concentrations of active plasma renin measured in normotensive subjects were between 7 and 40 ng/L.


1998 ◽  
Vol 83 (12) ◽  
pp. 1279-1288 ◽  
Author(s):  
Yan Yan ◽  
Rong Chen ◽  
Tina Pitarresi ◽  
Curt D. Sigmund ◽  
Kenneth W. Gross ◽  
...  

1984 ◽  
Vol 66 (5) ◽  
pp. 545-549 ◽  
Author(s):  
D. McAreavey ◽  
W. B. Brown ◽  
G. D. Murray ◽  
J. I. S. Robertson

1. Exchangeable sodium (NaE), plasma active renin concentration and blood pressure were measured in rats with a sole remaining kidney before and after the development of hypertension induced by clipping of the single renal artery and again after unclipping. 2. Control observations were made in sham-clipped and sham-unclipped uninephrectomized rats. 3. Renal artery clipping caused hypertension and expansion of NaE, the latter being sustained throughout the 6 weeks during which the renal artery was constricted. 4. Hypertension in the clipped rats was progressive over 6 weeks, whereas the expansion of NaE was not; thus the two measurements were not significantly correlated. 5. Two rats which remained normotensive after clipping did not show expansion of NaE. 6. Plasma active renin was elevated in comparison with the sham-clipped controls on the day after clipping, but not thereafter. 7. Unclipping in hypertensive rats was followed by a return of NaE and blood pressure to control values. 8. Both the sustained expansion of NaE and the transient rise in active renin probably contribute to the development of hypertension in this model, but neither alone nor together do they provide a full satisfactory explanation.


1989 ◽  
Vol 67 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Gregory M. T. Hare ◽  
Arlene Y. Loh ◽  
Daniel H. Osmond

Venous occlusion of the left arm in consenting men was induced for 10 or 20 min to stimulate local fibrinolytic and other proteases, thereby favouring the conversion of prorenin to renin. Using the two techniques cryoactivation and tryptic activation, we found that plasma active renin increased significantly after such occlusion (10 and 20 min) while prorenin rose more convincingly and progressively from 10 to 20 min. The renin increase can be partially attributed to hemoconcentration, but in vivo production and (or) local activation of prorenin to renin cannot be excluded. The prorenin rise can apparently be attributed to local extrarenal production, and not to hemoconcentration or influx, since it was progressive and neither prorenin nor renin levels were raised at all in blood circulating outside the occluded arm. Prekallikrein and plasminogen levels were elevated in occlusion plasmas, but responsibility of these enzyme systems for any enhanced activation of prorenin was not established. The trypsin inhibitory capacity was also elevated, increasing the requirement of trypsin to achieve optimal activation of prorenin, but not changing the prorenin estimate itself. Thus, prorenin appears to be released extrarenally, within the vasculature of an occluded arm, while in vitro evidence suggests that the mechanisms for its activation were stimulated. The importance of such extrarenal production and activation of prorenin for renin production under other physiological or pathophysiological conditions remains to be determined.Key words: venous occlusion, extrarenal prorenin, production, activation.


1979 ◽  
Vol 57 (s5) ◽  
pp. 105s-108s ◽  
Author(s):  
J. Ménard ◽  
P. W. N'goc ◽  
J. Bariety ◽  
P. T. Guyenne ◽  
P. Corvol

1. Highly specific antibodies to human renin were prepared in rabbits and used for the preparation of a renin-free substrate, the direct radioimmunoassay of renin in plasma and kidneys, and the localization of renin with fluoresceinated antibodies. 2. In a patient with a partially infarcted kidney, plasma renin activity was increased, and could be activated by acid. The direct measurement of plasma renin by radioimmunoassay gave identical values before and after acidification. 3. In the ischaemic part of the kidney, renin content was high, both by the enzymatic and the direct method of measurement. It was low in the non-ischaemic part of the kidney. 4. All afferent and some interlobular arteries of the obsolescent glomeruli were stained with fluoresceinated anti-renin antibodies. In the non-ischaemic area, the juxtaglomerular apparatus did not stain. 5. Renin can now be measured in human plasma and kidney as an entity, by a specific radioimmunoassay. A direct investigation of this intrarenal hormone is now possible at the renal tissue level.


1987 ◽  
Vol 9 (8-9) ◽  
pp. 1383-1390 ◽  
Author(s):  
P. Dessì-fulgheri ◽  
F. Cocco ◽  
N. Glorioso ◽  
F. Bandiera ◽  
P. Madeddu ◽  
...  

1987 ◽  
Vol 252 (4) ◽  
pp. E509-E518
Author(s):  
N. Glorioso ◽  
C. Troffa ◽  
J. H. Laragh ◽  
S. A. Atlas ◽  
D. Marion ◽  
...  

Inactive renin, prorenin, is found in high concentrations in human plasma. We report herein the characteristics of trypsin-activated inactive renin from cat kidney and plasma. Cat and human plasma inactive renin were activated by similar concentrations of trypsin. As in humans, there was more inactive than active renin in cat plasma; also, inactive renin was low but detectable after nephrectomy. Trypsin-activated renal inactive renin, purified on Cibacron blue agarose and pepstatin-amino-hexyl-Sepharose chromatography, was inhibited by pepstatin and by a renin inhibitor similarly to cat and human active renins. The pH optimum of cat renin was biphasic: the higher peak of active renin was at pH 5.7, whereas that of activated inactive renin was at pH 7.5. As in humans, active and inactive plasma renin increased during sodium depletion and inactive renin increased during beta-adrenergic blockade, while active renin decreased. These results demonstrate that cat inactive renin is similar to human prorenin. Therefore, the cat may be a useful model for the study of prorenin.


1996 ◽  
Vol 91 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Justin C. Konje ◽  
Stephen C. Bell ◽  
James J. Morton ◽  
Richard De Chazal ◽  
David J. Taylor

1. This study was designed to examine the changes in kidney morphometry during gestation in fetuses that were either appropriate or small for gestational age and the relationship between umbilical vein plasma active renin and kidney morphometry. 2. Serial ultrasound measurements of various morphometric and renal indices were performed in a cohort of 87 singleton fetuses from 22 to 38 weeks gestation. Blood was collected from the umbilical vein at delivery and active renin was measured from the plasma based on angiotensinogen I generated during incubation with plasma and ox renin substrate. 3. Growth in the longitudinal plane of fetal kidneys was similar in the small- and appropriate-for-gestational age groups; however, growth in the anterio-posterior, transverse and circumference planes of the kidneys was significantly slower in the small-for-gestational-age group after 26 weeks gestation. Differences in growth rate in the two groups were most marked between 26 and 34 weeks and persisted until delivery when the anterior-posterior diameter was significantly larger (P < 0.00001) in the appropriate-for-gestational-age group (26.1 ± 2.5 mm compared with 19.8 ± 2.6 mm). The mean umbilical vein active plasma renin concentration at delivery was significantly higher (P < 0.05) in the small-for-gestational-age group (274.4 ± 32.9 μ-units/ml plasma) than in the appropriate-for-gestational-age group (164.9 ± 28.3 μ-units/ml plasma). In addition, there were statistically significant inverse correlations between renin concentration and birthweight (r = − 0.55, P < 0.001) and between renin concentration and kidney anterior-posterior diameter (r = −0.67, P < 0.001). 4. Fetal renal growth was slower in small than in appropriate-for-gestational-age fetuses. The period of 26–34 weeks gestation was that during which maximum fetal renal growth occurred. Umbilical vein plasma renin levels were higher in small-for-gestational-age fetuses. The findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension. We suggest that 26 to 34 weeks could be the ‘critical period’ during which the insult that leads to in-utero programming for the development of adult hypertension occurs.


1987 ◽  
Vol 252 (1) ◽  
pp. F32-F38 ◽  
Author(s):  
D. Chansel ◽  
J. C. Dussaule ◽  
N. Ardaillou ◽  
R. Ardaillou

Renin activity was measured in the incubation medium, and the cellular extract of human mesangial cells, which had been cultured in the presence of renin-free human plasma (three kidneys; 4-7 passages). Active renin and total renin obtained after trypsin treatment was estimated by radioimmunoassay of angiotensin I using renin-free human plasma as a substrate. Mesangial cell renin had characteristics similar to those of standard human renin; optimum enzymatic activity at pH 5.8, marked inhibition in the presence of two (monoclonal and polyclonal) human renin-specific antibodies and of SR 42128, a new potent statine-containing renin inhibitory peptide. The synthetic capability of the mesangial cells varied markedly with the original kidney (1-49 and 0.3-0.9 ng X h-1 X mg-1 for total renin in the medium and the cellular extract respectively). Renin was secreted mainly as inactive renin. Prostaglandin E2 (PGE2) and carba-prostaglandin I2 (PGI2) (a stable analogue) produced a dose-dependent (0.1-1.10 microM) increase in renin activity in both the cellular extract and the culture medium. Isoproterenol (200 microM) increased renin activity only in the medium. The effects of these agonists were more marked on inactive than on active renin. These results demonstrate that cultured human mesangial cells synthesize and release renin in a stable manner over a long period of culture, thus providing a useful tool for the in vitro study of renin secretion and its control.


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