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P Corvol

Publications and source records attributed to P Corvol.

At least 343 records · Page 19Linked to original sources
PubMed1987

Regulation of prorenin secretion in cultured human transfected juxtaglomerular cells.

The regulation of renin secretion was studied in continuous culture of human juxtaglomerular cells (JGC), which provided a permanent source of human renin production (Pinet, F., M. T. Corvol, F. Dench, J. Bourguignon, J. Feunteun, J. Ménard, and P. Corvol, 1985, Proc. Natl. Acad. Sci. USA, 82:8503-8507). 95% of the renin species secreted was prorenin, and therefore this study concerned primarily prorenin secretion. Renin production was stable, since the cells had been maintained in culture for more than two years. In culture, these human cells formed colonies of smooth musclelike cells, and electron microscopy showed the presence of cytoskeleton structures including myofibrils and attachment bodies. This human model was used to investigate the control of prorenin secretion in vitro at cellular level. Various pharmacological agents known to stimulate or inhibit renin secretion were tested in the cell cultures. The variations in prorenin secretion were measured in the supernatant. Forskolin, an independent receptor activator of adenylate cyclase, stimulated prorenin secretion in a dose-dependent manner and this stimulation was mediated by 3',5' cyclic-AMP (cAMP). Angiotensin II (AII) was found to inhibit prorenin secretion directly in a dose-dependent manner and atrial natriuretic factor (ANF), whose effects on human JGC were characterized for the first time, was also shown to exert such inhibition. When the effects of this inhibition by AII and ANF were tested on forskolin-mediated stimulation of prorenin secretion, the latter was inhibited and no change occurred in cAMP release. When JGC were treated with histamine, bradykinin, or one or two bradykinin analogues, the responses suggested that in these cells, H2-histamine receptors and kinin receptors are dependent on adenylate cyclase. One peptide, substance P, had an inhibitory effect on prorenin secretion but it was less important than AII and ANF. The present results demonstrate that the adenylate cyclase system of human JGC remains intact during culture and supports the hypothesis that cAMP is the second messenger and Cai2+, the final messenger involved in renin secretion. The cell system used here permits the evaluation of cellular responses and intracellular events in granulated cells in a human model.

Angiotensin II↗
PubMed1987

Effect of mestranol on cell proliferation and angiotensinogen production in HepG2 cells: relation with the cell cycle and action of tamoxifen.

The effects of the estrogen analog mestranol and of the antiestrogen tamoxifen on cell growth and the rate of angiotensinogen production were investigated in HepG2 cells, an hepato-carcinoma cell line of human origin. After 36 h of cell contact with high concentration of mestranol, a (10(-5) M) dose increased by 2-fold the rate of proliferation of HepG2 while reducing angiotensinogen production to below control level. Mestranol at 10(-6) M preferentially stimulated angiotensinogen production 5-fold, whereas cell growth rate was slightly increased. Comparable results were obtained for thymidine uptake in the course of the cell cycle, with a maximum increase for 10(-5) M mestranol, and an increase of angiotensinogen production for 10(-6) M mestranol. At 10(-6) M, tamoxifen acted as a pure antagonist by strongly inhibiting the stimulatory effect of mestranol and reducing angiotensinogen production to below the control level within 60 h. Tamoxifen did not affect the growth rate of HepG2 cells, either when administered alone or together with an equimolar concentration of mestranol.

Angiotensinogen↗
PubMed1987

Liver angiotensinogen synthesis and release during captopril treatment in sodium-depleted rats.

In vivo generation of angiotensins depends upon both plasma renin and angiotensinogen concentrations. Those factors which may influence hepatic angiotensinogen synthesis and release were examined. We have evaluated in vivo the effects of converting enzyme inhibition on several plasma renin-angiotensin system components, and, using an in vitro preparation of liver slices, we also investigated the effects of converting enzyme inhibition on the synthesis and release of hepatic angiotensinogen. Angiotensinogen concentrations were determined by two different methods. The first was an indirect enzymatic assay which measures the amount of angiotensin I liberated from plasma by an excess of renin. The second was a direct RIA that measures both angiotensinogen and its inactive residue the des-angiotensin I-angiotensinogen. The difference between the methods represents the circulating levels of des-angiotensin I-angiotensinogen. Captopril administration in sodium-depleted rats increased plasma concentrations of renin, des-angiotensin I-angiotensinogen, and angiotensin I and decreased plasma angiotensinogen concentration measured by both methods. Plasma des-angiotensin I-angiotensinogen was significantly correlated to plasma renin concentration, which suggests an increase in the consumption of angiotensinogen when the renin secretion is extremely increased. The angiotensinogen liver content and in vitro angiotensinogen release were decreased in sodium-depleted rats treated with a converting enzyme inhibitor, and these parameters were negatively correlated to in vivo plasma levels of renin, angiotensin I, and des-angiotensin I-angiotensinogen. They were positively correlated to plasma angiotensinogen concentration measured by the indirect assay. These data suggest that captopril administration during sodium depletion has two simultaneous effects: it increases angiotensinogen consumption and second, decreases angiotensinogen production and release.

Aldosterone↗
PubMed1987

Measurement of active renin by the 4G1 anti-human renin monoclonal antibody.

Three monoclonal human renin antibodies have been selected to settle two immunoradiometric assays of human plasma renin (IRMA). The first pair of antibodies 3E8-4G1 recognizes exclusively active renin (AR), as demonstrated by the lack of increase either of the number of AR molecules or the renin enzymatic activity, when plasma is set free of inactive renin (IR) by immunoaffinity chromatography with human renin prosegment monoclonal antibody. The second pair of monoclonal antibodies 4E1-3E8 gives results which are very significantly correlated to those obtained with the 3E8-4G1 pair after trypsin activation. The standardization of renin measurements with use of monoclonal antibodies, and the standardization of renin will allow the exchange of comparable informations between the various laboratories involved in the investigation of the renin-angiotensin system in humans.

Antibodies, Monoclonal↗
PubMed1987

Monoclonal antibodies to human angiotensinogen: development of an ELISA for measurement of hepatocyte cultured cells content.

We have prepared and purified a rabbit polyclonal antibody (PcAb) and two mouse monoclonal antibodies (McAbs) against human angiotensinogen. The PcAb (Kd: 4.0 X 10(-12) M) inhibits 50% of the hydrolytic activity of renin on angiotensinogen, at a final dilution of 1:800. The two monoclonal antibodies (Kd: 5.0 X 10(-11) and 9.0 X 10(-13) M) do not inhibit the enzymatic reaction. None of the antibodies showed displacement of 125l-labeled angiotensinogen by angiotensin I, angiotensin II or human tetradecapeptide. The polyclonal antibodies recognize marmoset and baboon angiotensinogen with an affinity 10(3)lower than that of the human angiotensinogen, whereas the McAbs do not recognize primate angiotensinogen. Since the two monoclonal antibodies recognize different epitopes of the human angiotensinogen molecule than the polyclonal antibody, it is therefore possible to use them in various sandwich assays as ELISA. Thus, we have developed a liquid phase radioimmunoassay and an ELISA which allowed to measure human plasma angiotensinogen, under several pathophysiological conditions, and that produced by human hepatocyte cells in culture (HepG2).

Angiotensinogen↗
PubMed1987

Efficacy and influence on quality of life of enalapril as a first step treatment of hypertension.

205 patients with mild to moderate uncomplicated hypertension participated in a six-month double-blind parallel study performed in a unique center. After a two-week single-blind placebo period, the patients were randomly allocated to receive either Enalapril 20 mg once-a-day or placebo as the first step treatment. They were then followed-up every two weeks and successive doses of hydrochlorothiazide, oxprenolol, and dihydralazine were added until the diastolic pressure was lower than 90 mmHg. After six months, the systolic and diastolic blood pressures were lower in the Enalapril than in the control group (129/82 +/- 12/6 mmHg versus 136/86 +/- 10/5 mmHg; p less than 0.001). Drug withdrawal was necessary for 8 patients in the Enalapril group and for 16 patients in the control group (p less than 0.05). The number of daily tablets was 2.7 +/- 1.8 in the Enalapril group and 4.4 +/- 2.4 in the control group (p less than 0.01). Therefore, a stepped-care program based on Enalapril appears significantly more effective than a stepped-care program based on a diuretic.

Adult↗
PubMed1987

[Definition and consequences of blocking the renin-angiotensin system by converting enzyme inhibition].

46 patients (39 males), mean age 51 years (range 33-66), were randomly allocated to two different groups of treatment if their diastolic blood pressure was superior to 90 mmHg after a one-month treatment by 20 mg of enalapril. In the first group (ENA), 23 patients were given higher dosages of enalapril (40 and, if necessary 60 mg once-a-day). In the second group (HCTZ) 23 patients were given enalapril 20 mg and hydrochlorothiazide 25 and, if necessary, 50 mg once-a-day. Dosages were eventually increased after 2 weeks and evaluation of the results was performed after 4 weeks on treatment. Blood pressure was monitored in the supine position, at 3 minutes interval for thirty minutes, by an automatic device based on oscillometric method. Two successive measurements with a standard sphygmomanometer were performed by the physician at the end of the recording. No patient withdrew from the study nor was lost to follow-up. At the end of the study, 14 patients in the ENA group were receiving enalapril 60 mg once-a-day and 8 patients in the HCTZ group were receiving 50 mg of hydrochlorothiazide. Blood pressure was significantly lower in teh HCTZ group with the automatic device (130 +/- 9/80 +/- 8 vs 141 +/- 5/86 +/- 8 mmHg, p less than 0.01/p less than 0.05) and with the sphygmomanometer (134 +/- 10/89 +/- 6 vs 149 +/- 16/94 +/- 5 mmHg, p less than 0.001/p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Consequences of renal morphologic damage induced by inhibition of converting enzyme in rat renovascular hypertension.

The consequences of morphologic changes in the kidney distal to a stenosis induced by chronic administration of a converting enzyme inhibitor were determined after induction of experimental renovascular hypertension in rats. The relationship between changes in morphology in the clipped kidney and diuresis, creatinine, and mortality was studied by converting a two-kidney, one-clip model into a one-kidney, one-clip model after 1 month of converting enzyme inhibition. The right renal artery was constricted with a clip of 0.2 mm diameter to increase blood pressure, the left kidney was left untouched. After 1 month, systolic blood pressure had increased to 173 +/- 27 mm Hg in the clipped animals (n = 47) compared with 139 +/- 8 mm Hg in sham-operated animals (n = 15; group 1). An inhibitor of angiotensin-converting enzyme, MK421 (2 mg/kg, po), or an equivalent volume of vehicle was then administered daily for 1 month. After treatment with the converting enzyme inhibitor, blood pressure (148 +/- 28 mm Hg) was virtually identical with that of a sham-operated, vehicle-treated control group (145 +/- 16 mm Hg, n = 15), and was significantly lower than that of untreated hypertensive rats (186 +/- 30 mm Hg, n = 17) (group 2). The weight of the left kidney was increased in the untreated hypertensive animals as compared with sham-operated controls (1260 +/- 168 mg for group 2 versus 1075 +/- 100 mg for group 1). After treatment with MK421, the weight of the contralateral kidney (1472 +/- 190 mg) was further increased. After 1 month of treatment with MK421 or vehicle, the unclipped left kidney was removed from all animals. The treated animals were then randomly divided into two groups: one in which treatment with MK421 was stopped (treated/untreated, n = 24; group 3) and a second in which the treatment was continued (treated/treated, n = 23; group 4). The ability of the rats to excrete a water load of 15 ml was then examined 12 hours after removal of the unclipped left kidney. In the two groups of treated rats, the urinary excretion of the water load was decreased and frequency of oliguria was increased as compared with controls and hypertensive untreated rats. Survival rates were affected by the treatment: 3 deaths occurred in the hypertensive untreated group 2, 10 in the treated/untreated group 3, and 12 in the treated/treated group 4. The majority of these deaths could be attributed to renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

[Comparison of the effect of captopril and minoxidil on left ventricular mass. Results of a 6-month comparative double-blind test].

A randomised double blind study was performed in order to compare the cardiac effects of captopril and minoxidil in a subset of patients with severe primitive hypertension, uncontrolled (diastolic BP greater than 100 mmHg) by Metroprolol 200 mg/d and Furosemide 80 mg/d. 25 male pts completed the six month study, 33 pts having been excluded before randomisation (22 inadequate echoes) and 20 after randomisation (7 ambiguities on wall measurement). Average captopril dosage was 265 mg/d (150-300 mg), average minoxidil dosage was 19.6 mg/d (7.5-30 mg), dosages of Furosemide, Spironolactone and Metroprolol were similar in the two groups. Blood pressure decreased dramatically with both regimens (208/130 to 148/96 with captopril, 194/115 to 154/100 with minoxidil). Sokolow index was at the upper range of normal and decreased with both drugs. Cardiothoracic ratio decreased only with captopril. Echocardiograms were performed and read blindly at the end of the study. LV mass was measured according to Devereux, method. All patients had severe LVH. After 6 months posterior wall thickness decreased from 14.8 to 13.8 mm with captopril, remained stable from 14.1 to 14.9 mm with minoxidil, septal thickness decreased from 17.2 to 15.7 mm with captopril and remained stable (14.8 to 15.2 mm) with minoxidil. LV mass and mass index respectively decreased from 456 g and 232 g/m2 to 372 g and 190 g/m2 with captopril, and remained unchanged from 413 g and 215 g/m2 to 420 g and 218 g/m2 with minoxidil. Fractional shortening remained normal in both groups. Intra patients reproducibility was suboptimal because of difficulties in precise delineation of the endocardium in the severely hypertrophied ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[The decision to treat moderate hypertension: repetition of office visits or ambulatory monitoring of arterial pressure?].

World Health Organization (WHO) recommends antihypertensive therapy for mild to moderate hypertensive patients after 3 or more visits. We tested the hypothesis that an ambulatory blood pressure recording could also help to decide which patient need therapy. Blood pressure was measured in 89 essential, uncomplicated, hypertensive patients (diastolic (DBP): 90-110 mmHg, mean age: 41 +/- 13 years), with a mercury sphygmomanometer at 3 visits and with an ambulatory blood pressure recorder (Spacelabs) during 12 hours. According to WHO recommendations, patients were classified "WHO+" if they need a treatment (n = 44) and "WHO-" if they did not. The mean ambulatory DBP of each subject was compared to the arbitrary limit defined as the mean +2 standard deviations of the ambulatory DBP of a population of normotensive subjects in the same decade and same sex: patients with ambulatory DBP above this limit were defined "AMB+" (n = 27), the others were "AMB-". Ten patients were "WHO- AMB+" and 24 were "WHO+ AMB-". These discordances were independent of age, body weight, duration of hypertension, variability of ambulatory systolic and diastolic blood pressure defined by the standard deviation. By contrast, the difference between the measurements of the simultaneous blood pressure measurements performed with the two methods (mercury sphyngmomanometer and Spacelabs) 2 times by each patient could explain in part these discrepancies. The Spacelabs underestimates DBP measured with the mercury sphyngmomanometer in patients "AMB-" but not in patient "AMB+".(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Determination↗
PubMed1987

[Predictive factors of resistance to antihypertensive treatment].

Results of antihypertensive treatment were analyzed in a group of 5,209 hypertensive patients referred in two hypertension Clinics in Paris from 1976 to 1985. Patients were included in the study if they fulfilled the following criteria: 1) at least four visits in the clinic, 2) follow-up period greater than 6 months, 3) initial diastolic blood pressure greater than or equal to 90 mmHg and/or presence of an antihypertensive treatment. After a mean follow-up period of 43 months, blood pressure was reduced from 177/105 mmHg to 148/89 mmHg. However, in spite of at least two antihypertensive drugs, 16.7 p. 100 of these patients had a diastolic blood pressure above 95 mmHg at the end of the follow-up period and were defined as uncontrolled hypertensives (UH). By comparison with controlled hypertensives (CH), UH patients were more frequently males (67.9 vs 56.6 p. 100, p less than 0.001), had a greater known duration of hypertension (11.6 vs 8.7 years, p less than 0.001), and presented at the first visit with higher blood pressures (188/113 vs 174/103 mmHg, p less than 0.001/p less than 0.001), despite a higher rate of antihypertensive treatment (66.6 vs 53.8 p. cent, p less than 0.001), a higher ponderal index (26.3 vs 25.3/kg/m2, p less than 0.01) and a higher prevalence of end-organ damage (23.2 vs 16.3 p. 100, p less than 0.001). Sokolov index, serum creatinine and uric acid levels were higher among UH than among CH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1987

[Double-blind evaluation of slow-release nicardipine using different methods of blood pressure measurement. Predictive value of the acute response to intravenous nicardipine].

Forty hypertensive patients (diastolic greater than 95 mmHg) were included after 15 days of a single blind placebo period in a randomized placebo controlled double-blind study to assess the antihypertensive effect of a new galenic form of nicardipine (N) administered 50 mg b.i.d. for 3 weeks. They comprised 27 men and 13 women aged from 27 to 72 years (mean: 53 +/- 10). Blood pressure (BP) was measured in hospital before morning drug intake by an automatic recorder (Sentron) in supine position for 30 minutes (min) and by a mercury sphygmomanometer. Ambulatory BP was assessed by a portable patient activated recorder (Remler 2000). Mercury sphygmomanometer supine BP under N fell from 160 +/- 21/104 +/- 6 mmHg to 151 +/- 14/98 +/- 8 mmHg (n = 20; p less than 0.01/p less than 0.01) whereas BP under placebo (P) was respectively 158 +/- 14/103 +/- 6 mmHg and 156 +/- 20/102 +/- 9 mmHg (NS). Sentron BP under N fell from 158 +/- 17/96 +/- 8 mmHg to 148 +/- 13/90 +/- 7 mmHg (p less than 0.001/p less than 0.01) with no BP change under P (152 +/- 12/93 +/- 7 mmHg to 151 +/- 14/93 +/- 8 mmHg NS). BP recorder every 30 min for 12 hours revealed a decrease under N (160 +/- 18/105 +/- 10 mmHg to 142 +/- 16/94 +/- 10 mmHg; p less than 0.001/p less than 0.001) with a placebo effect in the control group on the diastolic BP (160 +/- 15/103 +/- 7 mmHg to 156 +/- 16/100 +/- 8 mmHg/NS/p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Results of the surgical treatment of Conn's adenomas].

During the last 10 years we operated on 69 Conn's adenomas of which 59 were followed up for a mean period of 16 months (range: 3-96 months). Surgery cured the hypertension (blood pressure less than 140/90) in 47 p. 100 of the patients. Improved blood pressure (systolic: mean = 46 mmHg; range 0-135 mmHg and diastolic: mean = 25 mmHg; range 0-66 mmHg) was noted in another 47 p. 100 of patients whereas no blood pressure change was noted in 3 patients. Biological primary aldosteronism was found post-operatively in 2 of these 3 patients and also in one whose hypertension was improved. In this last patient plus the three unimproved by surgery, small tumours (less than 10 mm) were found and co-existnt multifocal hyperplasia was found in the 2 patients who had had an adrenalectomy. Fifty-one patients were treated pre-operatively by spironolactone (SP) alone (3.2 +/- 1.3 mg/kg) for a mean period of 6.8 weeks (range: 3 to 20 weeks). Only 2 of the 24 patients controlled by SP were not cured by surgery and one of them had persistnt primary aldosteronism. Conversely, 3 of the 27 uncontrolled by SP were cured post-operatively, and these exceptions could be due to the weak dose of SP (n = 2) and an observance problem (n = 1). Patients cured by surgery had shorter duration of hypertension (4.3 +/- 3.0 years vs 10.1 +/- 8.1; p less than 0.01) and lower diastolic pressure (111 +/- 14 mmHg vs 121 +/- 12; p less than 0.01) than uncured patients. No significant difference between these two groups was observed with respect to systolic pressure, age, sex, plasma potassium, plasma renin activity and plasma aldosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1987

Direct radioimmunoassay for rat high molecular weight kininogen. Measurement of immunoreactive high molecular weight kininogen in normal and kininogen deficient plasma.

A direct radioimmunoassay (RIA) for rat high molecular weight kininogen (HMW Kg) was developed that enabled us to detect 71 fmol/ml of HMW Kg. The antibodies did not crossreact in the RIA with up to 5 nmol of purified rat alpha 1 cysteine proteinase inhibitor (T-kininogen). When various quantities of pure HMW Kg were either quantified by the RIA or by the measurement of kinin contents determined after trypsin hydrolysis, identical values were obtained by both methods. This RIA allowed the measurement of HMW Kg in 0.015 to 1 microliter of rat plasma. HMW Kg levels in plasma of Wistar rats and in Brown Norway rats of the Orlean Strain (BN/Orl) were 1.52 +/- 0.05 (n = 6) and 2.050 +/- 0.015 (n = 8) nmol/ml respectively. In the Brown Norway rats of the Katholiek strain (BN/Kat) that are considered to be deficient in HMW Kg, immunoreactive HMW Kg levels were less than 2% of those of the BN/Orl rats. These results confirm that the BN/Kat animals have a molecular defect in HMW Kg.

Animals↗
PubMed1986

Analysis of inactive renin by renin profragment monoclonal antibodies.

Two peptides were synthesized, corresponding to the sequences (-19 to -7) and (-26 to -17) of the prorenin prosegment. Monoclonal antibodies were raised to these sequences and used to characterize human plasma inactive renin. Only anti (-19 to -7) reacted with inactive renin, as measured by direct assay or affinity chromatography. The data were used to evaluate two possible inactive renin stuctures: plasma inactive renin is a truncated prorenin lacking the prosegment N-terminal portion; its spatial conformation masks the N-terminal extremity, preventing interaction of this region with specific antibodies.

Antibodies, Monoclonal↗