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J Ménard

Publications and source records attributed to J Ménard.

At least 181 records · Page 10Linked to original sources

Direct immunometric assay of active renin in human plasma.

None of the methods currently available can detect the small numbers of active renin (AR) molecules present in plasma. Among seven monoclonal antibodies (Ab), two Abs were selected which did not recognize the same epitope and could be used in a sandwich assay. The first monoclonal Ab, 3E8, binds soluble renin (B 50% = 1 x 10(-10) mol/l) and does not inhibit its enzymatic activity. It was coupled to magnetic beads (Magnogel) and was used to trap both active and inactive renin from 250 microliters plasma. The second Ab, 4G1, binds renin (B 50% = 3.5 x 10(-10) mol/l), inhibits its enzymatic activity, and recognizes inactive renin less than AR. It was iodinated and used to detect AR trapped on Magnogel by the first Ab during a 4-h incubation. The assay can detect 16 pg/ml in human plasma and is highly reproducible. The AR level of 15 normotensive subjects, aged 20-45 years, in an upright posture and on a normal sodium intake, was found to be 41 +/- 18 pg/ml (MRC renin standard). The plasmas were trypsin-activated and their total renin levels were measured with the same pair of monoclonal Abs. The mean value of 286 +/- 142 pg/ml is similar to the value obtained by other assay systems which measure total renin with Abs recognizing both active and inactive renin. The direct measurement of AR provides a convenient and standardized method, since the production of the two monoclonal Abs is unlimited.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Predictability and prevention of hypokalemia induced by hydrochlorothiazide].

In a double blind study, 104 hypertensive patients were randomly allocated to two different stepped care programs for 6 months. Following a placebo run-in-phase, patients were given either Enalapril (EN) 20 mg once-a-day, or a Placebo (PL). Drugs were added as follow in a parallel stepwise sequence, until the goal blood pressure was obtained. First Hydrochlorothiazide (HCTZ) and then, if necessary, Oxprenolol (OXP) and Dihydralazine (DIH). The two goals of this study were to lower diastolic blood pressure below 90 mmHg and to maintain plasma potassium above 3.5 mmol/l. Amiloride was prescribed if plasma potassium was lower than 3.5 mmol/l. At the end of the study the EN group's blood pressure was 130 +/- 12/83 +/- 6 mmHg, the tablet's daily number was 2.6 +/- 1.8 and Amiloride was necessary in 15 patients. These parameters were significantly different from those observed in the Pl group (BP: 136 +/- 9/87 +/- 5 mmHg, tablets 4.2 +/- 2.4; amiloride necessary in 34 patients). The effects of HCTZ were evaluated in 32 patients previously treated by EN compared to 39 patients receiving PL. The converting enzyme inhibition minimized the fall in plasma potassium induced by HCTZ (3.6 t +/- 0.4 vs 3.3 +/- 0.5 mmol/l, p less than 0.05). Related to the HCTZ dose (mg/kg), the plasma potassium fall is lower in the EN group (0.46 +/- 1.1) than in the PL group (0.94 +/- 0.9, p less than 0.05). The plasma potassium reduction could not be predicted by age, plasma renin activity, plasma and urinary aldosterone or urinary kallikrein.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Influence of educational and sociocultural factors on hypertension care.

The influence of occupational category (OC) on the prevalence of hypertension (HT) and cardiovascular risk factors and on their management was studied in Paris in a general population and in a series of patients followed up in two university hospital hypertension clinics. Three OCs were defined as follows: high executives and members of liberal professions middle executives and clerks and manual workers. In the general population, the prevalence of HT was positively associated with OC, and ranged from 12.8% (1) to 19.3% (3). Body Mass Index (BMI) and tobacco and alcohol consumption were higher in category 3. Exposure to noise and assembly-line work raised blood pressure. Of the hypertensive subjects, 60% were aware of their illness, independently of OC, but the percentage of treated hypertensive subjects at examination and their compliance with treatment were significantly and negatively correlated with OC. In the hypertension departments, more category 1 and 2 patients were examined than expected for a theoretical French population of similar sex, age and geographical distribution. By contrast, clerks and manual workers were under-represented. BMI was higher in OC 3 than in OC 1, in both sexes. Cigarette consumption was higher in OC 1 than in OC 3 in males only. Permanent teaching staff members examined more people from OC 1 than the other physicians did. Drop-out rates at 1, 2 and 3 years were higher in OC 3 than OC 1. The problems of compliance with antihypertensive treatment were more frequent in OC 3 patients than in those in the other categories.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Variability of arterial pressure during consultation. Effect of the physician and patient characteristics].

The decision to treat patients with high blood pressure depends largely on the level of pressure. However, a major difficulty is the great variability of blood pressure level in any individual patient. From May 1st 84 to July 1st 84, 259 patients were referred for the first time to the outpatient clinic and were seen by one of the four physicians. Before the consultation and during the medical interrogatory 18 + 8 measures were performed every 2 minutes by an automatic device using the oscillometric method. The physician measured the blood pressure (BP) using the auscultatory method according to the WHO recommendations, after the medical interrogatory. Measured by the physician, BP was 174 + 28/104 + 15 mmHg. Measured by the automatic device, BP was 158 + 22/94 + 14 mmHg. The correlation between the two methods was excellent (SBP: r = 0.88 and DBP: r = 0.82; p less than 0.001) but the mean of BPs automatically recorded was significantly lower (-15/11 mmHg) than the BP measured by the physician. The mean of the highest BPs recorded by the oscillometric method (179 + 26/108 + 16) was slightly higher than the BP recorded by the physicians. Blood pressure variability was defined by the standard error (SE) of BPs measured by the automatic device (SE: 11 + 4/7 + 2). SE was positively correlated with the BP level measured by the physician or by the machine and with the heart rate variability for both SBP and DBP, and with patient's age for SBP only. SE was negatively correlated with the coffee consumption and the tobacco consumption. Blood pressure variability was significantly higher in men than in women (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Arterial hypertension in heart transplant patients treated with cyclosporin].

Amongst 40 patients undergoing cardiac transplantation between 1981 and 1984 and treated with cyclosporin A, 23 had hypertension. Fifteen of these patients, aged 39 years (16-57 years), without cardiac failure, treated with 8 +/- 3 mg kg-1 d-1 of cyclosporin A and 0.27 +/- 0.1 mg kg-1 d-1 of prednisolone were studied on average 288 days after transplantation (63-788 days). Blood pressure in the out-patients department of these 15 patients was 164 +/- 14/112 +/- 13 mmHg, in the absence of any antihypertensive treatment for more than 15 days, with a urinary sodium of 104 +/- 48 mEq/d and a urinary potassium of 55 +/- 13 mEq/d (mean +/- standard deviation). Two abnormalities accompany the raised blood pressure: a reduced creatinine clearance of 63 +/- 30 ml min-1 and an increased plasma volume of 445 +/- 686 ml (p less than 0.05) with reference to Hurley's norms (1975). By contrast, urinary excretion of VMA and metanephrines were invariably normal. Plasma renin activity (PRA) was normal in a lying position (1.02 +/- 0.42 ng ml-1 h-1) and after orthostatic stimulation (2.55 +/- 1.31 ng ml-1 h-1). Renin release was not stimulated by acute inhibition of converting enzyme (1.11 +/- 0.70 ng ml-1 h-1). Plasma aldosterone (110 +/- 52 pg ml-1), plasma angiotensinogen (924 +/- 213 ng/ml) and converting enzyme activity (30 +/- 6 mU ml-1) were normal. In these patients with a denervated heart, the orthostatic position increased heart rate from 85 +/- 11 to 93 +/- 12 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Kallikrein secretion by the isolated perfused rat kidney. Role of perfusion pressure and the renin-angiotensin system].

The isolated perfused rat kidney (IPRK) releases kallikrein in urine and renin in perfusate. We have previously shown (Kidney Int 24: 58-65, 1983) and confirm here that kallikrein, as well as renin releases are influenced by changes in renal hemodynamics in this model: a rise in perfusion pressure (PP) from 80 to 98 mmHg increases renal perfusate flow (RPF) by 48 +/- 3 p. 100, inhibits renin release and stimulates kallikrein secretion to 234 +/- 84 p. 100 of control values (n = 8). Since the perfusate lacks angiotensinogen, we decided to study the effect on kallikrein of the reconstitution of the renin-angiotensin system in the IPRK by adding angiotensinogen + angiotensin converting enzyme (AG + ACE) to the perfusion medium. After AG + ACE, PP rose to 107 +/- 4 mmHg, RPF decreased by 82 +/- 3 p. 100 as a consequence of the vasoconstrictor effect of angiotensin II, and renin release was suppressed. Again kallikrein secretion was stimulated and increased to 333 +/- 153 p. 100 of control values (n = 4). It is concluded 1) that kallikrein release is influenced by changes in PP but not in RPF on the IPRK. 2) that reconstitution of the renin-angiotensin system by addition of AG + ACE to the perfusate leads to vasoconstriction, suppression of renin release and a marked increase in kallikrein secretion.

Animals↗

[Plasma renin and catecholamine activity in pheochromocytoma].

We have studied the renin aldosterone system and plasma catecholamines in 26 untreated patients with phaeochromocytoma, 21 untreated patients with primary hypertension, and in 10 normal volunteers. Blood pressure (mmHg), plasma renin activity (radioimmunoassay of angiotensin I, ng/ml/h), plasma concentrations of aldosterone (direct radioimmuno-assay, pg/ml), adrenaline and noradrenaline (radioenzymatic assay with catechol-O-methyl transferase, pg/ml) were measured after 1 h of supine rest, 5 mn upright and after walking 1 h. Seven patients with phaeochromocytoma were subsequently given 400 mg acebutolol bid for 3 days, and five were given 1 mg/kg captopril. Supine renin activity was higher in phaeochromocytoma than in primary hypertension and in volunteers (average 2.54, 1.03 and 0.85, F = 7.1, p less than .01) and rose higher after walking (mean increase 3.84, 1.19 and 0.68 respectively, F = 6.3, p less than .01). Aldosterone was higher after walking in phaeochromocytoma than in primary hypertension (534 vs 275 pg/ml, p = .03). Differences in renin and aldosterone could not be explained by age, natriuresis or plasma volume. Catecholamines were as expected much higher in phaeochromocytoma than in the other two groups (p less than .01). At variance with primary hypertensive and normal volunteers, renin was tightly correlated with noradrenaline in patients with phaeochromocytoma (r' = .54, r' = .60, and r' = .74 in supine position, after standing and after walking 1 h, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Renal segmental infarction: a cause of reversible malignant hypertension.

Five cases of accelerated or malignant hypertension which occurred in young adults within a few weeks of renal segmental infarction are reported here. Such infarction appears to give rise to a form of renovascular hypertension, the severity and sudden onset of which distinguishes it from renal fibrodysplasia, which is commonly observed in this age group. In three cases hypertension was corrected by nephrectomy. In two cases several months medical treatment was associated with remission of hypertension without surgery. It is therefore suggested that hypertension due to renal infarction, unlike that caused by fibromuscular dysplasia, may be managed by prolonged medical treatment.

Adult↗

[Comparison of the cardiac, renal and endocrine effects of converting enzyme inhibition with those of a classical triple therapy in experimental renal hypertension].

In the rat model of hypertension induced by a clip on the right renal artery, sparing the left kidney, we compared the efficacity and the endocrine, renal and cardiac effects of classical therapy (CT) of hypertension (Clonidine 0.2 mg/kg and Dihydralazine 15 mg/kg in 2 daily subcutaneous injections and Furosemide 30 mg/kg/day in the drinking water), with inhibition of the angiotensin converting enzyme with a new drug, the S-9490-3 (0.5 mg/kg in one daily administration). The untreated animals (HT: n = 12) had an average systolic blood pressure (SBP) of 215 +/- 32 mmHg. After 1 month' treatment, S-9490-3 (n = 13) lowers SBP to 144 +/- 32 mmHg compared to CT (n = 12) which lowered SBP to only 172 +/- 18 mmHg. The average plasma renin concentrations of the HT animals was four times the normal value (39 +/- 33 ng/ml/h) and both treatment regimes increased it further (S-9490-3: 129 +/- 65 ng/ml/h; CT: 97 +/- 73 ng/ml/h). Angiotensin levels fell in proportion to the increase in renin concentration. Plasma aldosterone was normalised by S-9490-3 (460 +/- 320 pg/ml) but remained as high after CT (850 +/- 650 pg/ml) as in the untreated HT animals (830 +/- 260 pg/ml). Despite the Furosemide, plasma volume increased significantly in the CT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Angiotensin I-converting enzyme in foetal membranes and chorionic cells in culture.

Angiotensin I-converting enzyme (ACE) is found in human amniotic fluid and foetal membranes taken during Caesarean sections at term. ACE contents are higher in the chorion than in the amnion. Cells cultured from chorion contain ACE together with renin. Chorionic ACE was inhibited by captopril and by an excess of anti-ACE immuneserum. It is concluded that extravascular ACE is present in the uteroplacental complex during pregnancy.

Amniotic Fluid↗

The role of the renin-angiotensin system in blood pressure regulation in normotensive animals and man.

The role of the renin-angiotensin system in the control of blood pressure in normal rodents, primates and man has been evaluated using inhibitors which block the system at various stages. Renin plays a major role in the maintenance of blood pressure under volume depletion. In subjects with a normal salt intake, the contribution of the renin-angiotensin system in maintaining blood pressure levels can be evaluated using angiotensin converting enzyme (ACE) inhibitors. The contribution of the renin-angiotensin system can now be evaluated more closely following the development of new substances which block the renin-angiotensinogen reaction. Available data strongly suggest that renin contributes to the maintenance of blood pressure levels in subjects with a normal salt intake, although to a lesser degree than in subjects on a low sodium intake. The renin-angiotensin system plays a role in the regulation of blood pressure levels in normal experimental animals and man--its importance depending on the state of sodium balance.

Angiotensin II↗

A double-blind randomized evaluation of converting enzyme inhibition as the first-step treatment of mild to moderate hypertension.

The new angiotensin converting enzyme inhibitor, enalapril (MK-421), was tested by a double-blind trial. Patients with uncomplicated essential hypertension were randomly allocated to one of two stepped-care treatment groups: enalapril 20 mg once-a-day, or placebo as the first step, followed when necessary by the successive addition of hydrochlorothiazide (25 and 50 mg), oxprenolol (160 and 320 mg) and dihydralazine (50 and 100 mg). Blood pressure was normalized in both groups, although the enalapril group showed lower systolic and diastolic blood pressures than the placebo group (systolic 130.5 +/- 12 versus 136.6 +/- 9 mmHg, P less than 0.01; diastolic 82.8 +/- 6 versus 87.0 +/- 5 mmHg, P less than 0.001). These results were obtained with a smaller number of tablets per day (2.6 +/- 1.8 versus 4.2 +/- 2.4 mmHg, P less than 0.0001). Plasma potassium was identical for both groups at the start of treatment. At the end of the study, it was significantly higher in the enalapril group than in the placebo group (4.1 +/- 0.3 versus 3.9 +/- 0.5 mmol/l; P less than 0.05). Spontaneous complaints were noted during the bi-weekly or monthly visit and were also expressed by patients completing a self-administered questionnaire. Differences in spontaneous complaints or in the symptoms evaluated by the questionnaire were not significant. The increase in the number of symptoms at the end of the study was greater in the placebo group than in the enalapril group, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renin inhibition by synthetic peptides related to mouse and human renin prosegments.

Recently the nucleotide sequences of the genes coding for mouse and human renins have been elucidated and the primary structures of the corresponding renin precursors deduced. The existence of a prosegment suggests that renin is biosynthesized as an inactive zymogen prorenin. Three peptides related to the region 11-19 of the mouse submaxillary prosegment have been synthesized and tested as inhibitors of pure mouse renin acting on a synthetic porcine substrate. Inhibition of renin activity was effective, with IC50s in the 10(-6) M range. Butyloxycarbonyl-leucyl-lysyl-lysyl-methionyl-proline methyl ester (15-19) was the most potent inhibitor with a K value of 2.3 X 10(-6) M at 37 degrees C in 0.5 M citrate/phosphate buffer (pH 6.0). Peptides 16-20 and 9-20 of the human renin prosegment and peptides 11-19 and 15-19 of the mouse prosegment were tested on human plasma renin activity and found to be inhibitory, with IC50s of 3 to 5 X 10(-4) M. These results demonstrate that the renin prosegment is a renin inhibitor and support the hypothesis that prorenin is an inactive zymogen.

Animals↗

A multirange ELISA for the measurement of plasma renin in humans and primates.

A sensitive solid phase enzyme-linked immunosorbent assay (ELISA) has been developed using two anti-human renin monoclonal antibodies, which were shown to bind both human as well as primate renin at two different epitopic sites. One monoclonal antibody (3-36-16) was used to coat each well of a 96 well microtitre plate in which renin, contained in 5 to 20 ul of plasma, was allowed to react. Plates were then incubated with the gamma globulin (gamma G) fraction of a rabbit anti-human renin serum followed by development with sheetp anti-rabbit gamma G conjugated to alkaline phosphatase. Quantification was carried out by the addition of the alkaline phosphatase substrate, p-nitrophenylphosphate, which produced a colorimetric reaction. The sensitivity of the assay is 25 pg ml-1. The method recognises both active and inactive renin from plasma, kidney, amniotic fluid and chorionic cells. Plasma renin can be measured within 6 hours when values are greater then 150 pg ml-1 or within 24 hours when plasma values are less than 150 pg ml-1. The ELISA has already been used to measure total immunoreactive renin in plasma obtained from patients with several forms of hypertension. The values ranged from 25 pg ml-1 in patients with primary aldosteronism to as large as 60 ng ml-1 in a patient with a renin-secreting tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Multicenter trials in the treatment of arterial hypertension. Socioeconomic repercussions].

The various therapeutic trials conducted throughout the world demonstrate the benefit of treatment even for a moderate elevation of diastolic pressure (90 or 95 mmHg). At this level of hypertension, treatment is more preventative than curative. This article discusses the benefits and the costs on the individual and collective scale in the context of two opposed strategies: mass treatment after a certain level of blood pressure or treatment of subjects at high risk of cardio-vascular disease. To achieve a collective benefit, all of the hypertensives defined in this way need to be detected, treated and followed-up in the long-term. Stimulation of the present medical system would appear to be more effective and less costly than the creation of specialized structures.

Adult↗

[Treatment of arterial hypertension. Comparative effectiveness of the day care hospital and classical hospitalization].

Four years of activity in the one-day hospital (ODH) and the several-day hospital care (SHC) of the Hypertension Clinic at the Hôpital Saint-Joseph, Paris, were evaluated and compared. All data were recorded using the computerized Artemis system. Evaluation was performed by means of two prospective studies: a controlled trial of 121 patients randomized to either ODH or SHC, and a prospective follow-up study of 633 patients. Criteria for admission to the controlled study were: diastolic BP between 95 and 120 mmHg, age between 30 and 65 years, no anti-hypertensive treatment at first visit, no major cardiovascular or renal complication and no suspicion of secondary hypertension. Similar criteria applied to the uncontrolled study. The results, assessed after 2 years, were the same in both studies, with a drop-out rate of about 15%, a mean diastolic BP lower than 95 mmHg in 80% of the patients and a bodyweight reduction of about 1 kg in obese patients. The percentage of smokers who stopped cigarette smoking was higher in the SHC groups than in the ODH groups. It is concluded that the ODH system is effective in the initial management of hypertensive patients but that greater educational efforts are needed to effectively reduce cigarette smoking in OHD patients and bodyweight excess in both OHD and SHC patients.

Adult↗