PubMed Health⌕ Search

Biomedical subjects

J Ménard

Publications and source records attributed to J Ménard.

At least 199 records · Page 11Linked to original sources
PubMed1983

Clonidine, acebutolol and their interaction in essential hypertension: effects on blood pressure and the control of water and electrolyte balance.

The effects of 0.5 mg of slow-release (sr) clonidine, 800 mg of acebutolol, and of both drugs combined on blood pressure and the water-salt balance were compared in 10 patients with essential hypertension. An initial placebo period was followed by three 72-h periods during which 5 patients were given sr-clonidine, acebutolol plus sr-clonidine, and acebutolol, respectively in that order whereas the other 5 received the same drugs in the opposite order. Placebo and active medications were given once a day, and the recorded variables were measured 24 h after the last intake. Sr-clonidine, acebutolol and their combined administration reduced mean blood pressure by 23, 16 and 39 mmHg, respectively, indicating first, that single daily doses of sr-clonidine and/or acebutolol constitute satisfactory antihypertensive treatments and second, that the interaction of these drugs is additive. All three treatments reduced plasma renin activity significantly and similarly. A reduction in plasma and urinary aldosterone was observed with sr-clonidine, and a decrease in plasma noradrenaline with the combined treatment. Both water diuresis and natriuresis rose significantly during combined therapy. The additive antihypertensive effects of sr-clonidine and acebutolol might be due to the parallel inhibition observed in the renin and sympathetic systems, and to the increase in natriuresis.

Acebutolol↗
PubMed1983

Biochemistry and regulation of angiotensinogen.

Angiotensin II and angiotensin III, the active peptides of the renin-angiotensin system, are produced by a cascade of enzymatic reactions, whose initial step is the reaction between renin and its substrate, angiotensinogen. In plasma, the concentration of angiotensinogen is a limiting factor: the Km of the enzymatic reaction is between 1 and 2 microM depending on the species. It is therefore of interest to measure its level in plasma and tissues and to examine the main factors which may influence its synthesis and release. The complete purification of angiotensinogen has made possible the preparation of specific antibodies which cross-react with both angiotensinogen and its residue, des-angio I-angiotensinogen, and are currently used in radioimmunoassays and immunohistochemical studies. A small amount of angiotensinogen is stored in hepatic cells, where it can be detected by immunofluorescence and measured by radioimmunoassay. It is also present in proximal tubular cells of the kidney, probably reabsorbed from glomerular filtrate, but it is absent from juxtaglomerular cells. Several hormones are able to increase liver synthesis of angiotensinogen and its release. Thyroxine, angiotensin II, dexamethasone, ethinyl-estradiol and binephrectomy increase both synthesis and release. Adrenalectomy and converting-enzyme inhibition are accompanied by an increased peripheral consumption of plasma angiotensinogen, and by accumulation of des-angio I-angiotensinogen whose metabolism and role are unknown. The major role of angiotensinogen in renal hemodynamics is demonstrated by its effects on the isolated perfused kidney, an experimental observation which parallels the clinical observation of women on estroprogestative therapy, whose renal blood flow is reduced, even in the absence of a detectable increase in their blood pressure. A better knowledge of renin substrate structure in various species is a necessary requirement for the design of inhibitory analogs of angiotensinogen which will have application for the treatment of hypertension and oedema.

Adrenalectomy↗
PubMed1983

Vascular effects and metabolism of angiotensins and their metabolites in the isolated perfused rat kidney.

The vascular effects of the injection of angiotensin I (AI), des-Asp1-angiotensin I (des-Asp1-AI), angiotensin II (AII), des-Asp1-angiotensin II ( (2-8)AII) and des-Asp1-Arg2-angiotensin II ( (3-8)AII) have been investigated in an isolated perfused rat kidney model, using a closed circuit system. The apparent half-life of these peptides was measured by AI and AII radioimmunoassays. Des-Asp1-AI is less potent than AI and has a shorter duration of action on perfusion pressure and renal flow. Up to 7.6% of circulating AI and 12.4% of circulating des-Asp1-AI are converted by the kidney to AII, (2-8)AII and other AII immunoreactive materials. This intrarenal conversion entirely explains the vasoconstrictor effects of these two peptides. The vasoconstrictor effects of (2-8)AII is similar to that of AII, but (2-8)AII has a shorter duration of action. At the doses injected, renin secretion is completely inhibited by AII and (2-8)AII, it is partially inhibited by AI, an effect which disappears when converting enzyme is inhibited. Des-Asp1-AI is a less potent inhibitor of renin secretion than AI, and (3-8)AII is devoid of any action on renin secretion. The apparent half-life of AI is 24.3 +/- 1.1 minutes, des-Asp1-AI: 20 to 23 minutes, AII: 19.6 +/- 1.8 minutes, (2-8)AII: 12 to 14.5 minutes and (3-8)AII: 12.5 to 13.5 minutes. Differences in the metabolism of these peptides may contribute to the differences of magnitude and duration of their vascular effects.

Angiotensin I↗
PubMed1983

Inhibition of renin in the primate Callithrix jacchus (common marmoset).

The effects of an antiserum against human kidney renin and of H-142, a peptide inhibitor of human renin, were studied in the primate Callithrix jacchus (common marmoset). In severely volume-depleted (low-salt diet and repetitive injections of furosemide), conscious marmosets, the antiserum reduced blood pressure to the same extent as the converting enzyme inhibitor teprotide (-31 +/- 7 SEM mmHg and -30 +/- 5 mmHg). In mildly volume-depleted (normal salt diet and single injection of furosemide), conscious marmosets, H-142 and teprotide induced a similar fall in blood pressure (-14 +/- 4 mmHg and -15 +/- 2 mmHg). When H-142 was infused after the injection of teprotide, it had no further effect on blood pressure. Conversely, teprotide was ineffective when injected during the infusion of H-142. These results show that in marmosets blood pressure can be lowered by specific inhibitors of human renin. A converting-enzyme inhibitor has similar effects. Hence the renin-angiotensin system appears to contribute significantly to the maintenance of blood pressure in conscious, volume-depleted marmosets.

Angiotensinogen↗
PubMed1983

The effects of converting enzyme inhibitors on plasma angiotensinogen and plasma aldosterone in sodium-depleted rats.

Plasma angiotensinogen was measured by two different methods in three groups of sodium-depleted rats: control rats, captopril-treated rats and enalapril-treated rats. The enzymatic method of measurement is an exhaustion technique which measures the amount of angiotensin I liberated from plasma by an excess of renin. Direct radioimmunoassay measures both angiotensinogen and its inactive residue, des-angio I-angiotensinogen, and the difference between the results of both methods can be used as an indirect measurement of plasma des-angio I-angiotensinogen. Both converting enzyme inhibitors decreased blood pressure, stimulated renin secretion, decreased plasma angiotensinogen and increased des-angio I-angiotensinogen. Plasma des-angio I-angiotensinogen levels were positively correlated with plasma renin levels. In converting enzyme inhibitor-treated rats, plasma aldosterone was slightly, but not significantly, lower than in control rats. Although plasma aldosterone was significantly correlated with plasma renin both in control rats and converting enzyme inhibitor-treated rats, plasma renin was elevated 10-fold in treated rats.

Aldosterone↗
PubMed1983

[Antinuclear antibodies and lupus induced during treatment of arterial hypertension. Role of beta-blockers and alpha-methyldopa].

Comparison of hypertensive patients receiving no treatment with subjects of the same age reveals the presence of antinuclear antibodies in twice as many of the former as the latter. Various antihypertensive drugs increase this prevalence. They may induce iatrogenic lupus. Alpha-methyldopa: the frequency of antinuclear bodies is three times greater than in untreated hypertensive patients. However there are no reported cases of clinical symptomatology of induced lupus. Beta-blockers. Practolol, acebutolol, labetalol, atenolol, timolol, metoprolol, pindolol and oxprenolol are suspected of increasing antinuclear antibodies. These drugs may be weak inducers of iatrogenic lupus when compared with major drugs: procainamide, high doses of hydralazine and D-penicillamine.

Adrenergic beta-Antagonists↗
PubMed1983

[Captopril-induced eruptions: occurrence over a 3-year period].

With an informatized sample of 123 patients taking Captopril and treated for a total duration of 1,321 month/patients, the frequency of the dermatological symptoms induced by the drug is related. Pruritus is found in 10,5 p. 100 and rashes in 2,4 p. 100 of cases. The results are compared with those of preceeding reports, although some authors have found a higher percentage because of highin doses of the drug. The clinical features of the rashes and the proposed mechanisms are also reported.

Adult↗
PubMed1983

[A new diagnostic test for primary tumoral hyperaldosteronism].

Plasma aldosterone levels were measured during two tests of inhibition in 31 hypertensive patients (13 essential hypertension, 6 bilateral adrenal hyperplasia and 12 documented Conn adenomas) on normal salt diets after withdrawal of all therapy: 1--before and after intravenous infusion of 2 I normal saline in two hours; 2--before and three hours after administration of 1 mg/kg of Captopril. Plasma aldosterone levels greater than 360 pmol/I after salt loading, or greater than 748 pmol/I after Captopril is characteristic of primary tumoral hyperaldosteronism. Apart from the rapidity of the test, Captopril is well-tolerated, does not require acute volume expansion and can be carried out in all forms of hypertension, even in severe cases.

Adenoma↗
PubMed1983

[Primary hyperaldosteronism: diagnostic value of the administration of a single dose of captopril].

The diagnosis of primary tumoral hyperaldosteronism is based on a series of hormonal parameters, measured under resting conditions and after stimulation. The results of the administration of a single dose of a converting enzyme inhibitor, Captopril (1 mg/kg body weight per os), can support this diagnosis. In contrast to essential hypertension and hyperaldosteronism due to bilateral adrenal hyperplasia, plasma aldosterone levels remain unchanged in tumoral hyperaldosteronism after administrating Captopril. This is a simple test which can be performed in a morning which clearly differentiated 8 cases of primary tumoral hyperaldosteronism from 6 cases of adrenal hyperplasia.

Adenoma↗
PubMed1983

Mouse submaxillary renin: a useful model for the study of renal renin.

The submaxillary gland of mouse contains a renin-like enzyme which represents as much as 5% of the total protein content. Its physico-chemical and enzymatic characteristics are similar to those of renal renin. Recently, the amino-acid sequence of the submaxillary pre-prorenin molecule has been deduced from the nucleotide sequence of the renin structural gene. A model for pre-prorenin processing into active renin has been proposed. Comparison of the structures of mouse submaxillary renin and of aspartyl proteases shows that renin belongs to this class of proteins and shares a similar catalytic site. Although the structure of renal renin is not yet known, preliminary studies suggest that the renal pro-enzyme is processed as the submaxillary enzyme. However, glycosylation would occur in the case of renal renin, whereas submaxillary renin is not glycosylated. Genetic studies and DNA hybridization experiments in mouse with high or low renin content in the submaxillary gland show that submaxillary renin in high renin producing strains results from a gene duplication. Submaxillary renin is therefore an isoenzyme and a useful model for the study of renal renin.

Amino Acid Sequence↗
PubMed1983

Effects of circulating renin substrate on renal function in isolated perfused rat kidney.

The effects of two different amounts of pure rat angiotensinogen were investigated in a closed circuit isolated perfused rat kidney. In response to angiotensinogen, circulating levels of angiotensin I (AI) and angiotensin II (AII) immunoreactive materials were found to increase in a time and dose-dependent manner. Vasoconstrictor and renin inhibitory effects were observed in parallel with the increase in AII. Glomerular filtration rate decreased after administration of angiotensinogen to a greater extent than renal flow and filtration fraction. The characterization by high performance liquid chromatography of peptides generated showed the liberation of AI, des-Asp1AI, AII and des-Asp1AII (AIII). These findings demonstrate that administration of angiotensinogen in an isolated perfused kidney model generates AI and that renal converting enzyme and aminopeptidases are able to convert AI to AII, AI to des-Asp1AI, and des-Asp1AI and/or AII to AIII. Changes in circulating level of angiotensinogen influence the activity of the renin-angiotensin system and, therefore, renal function.

Angiotensin I↗
PubMed1982

Direct radioimmunoassays of renin and renin substrate during converting-enzyme inhibition.

In 10 severely hypertensive patients, on a low sodium diet, converting enzyme inhibition increased plasma renin activity and decreased plasma renin substrate. The use of direct radioimmunoassays for both the enzyme and its substrate showed that the number of immunoreactive renin molecules increased from 11.3 +/- 4.9 to 31.7 +/- 25.3 pmol 1(-1) whereas the number of immunoreactive renin substrate molecules decreased from 1.04 +/- 0.35 to 0.74 +/- 0.16 mumol 1(-1). The direct radioimmunoassay for angiotensinogen gave higher values than the direct enzymatic assay, and during converting enzyme inhibition, the difference between both methods increased in proportion to the rise in circulating renin. It is concluded that the difference between the renin substrate radioimmunoassay, which measures angiotensinogen and des-angio I-angiotensinogen, and the renin substrate enzymatic assay which only measures "active" substrate, is an index of the increased consumption of renin substrate, in a situation where the fall in angiotensin II enhances renin release and decreases renin substrate release.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

[Changes in angiotensinogen and des-angiotensin I-angiotensinogen in man and rat upon inhibition of converting enzyme].

The effects of converting enzyme inhibition on plasma renin substrate concentration were studied in man and rat. This study use new direct radioimmunoassays of angiotensinogen completing the classical enzymatic methods. In human investigation converting enzyme is inhibited after Captopril treatment. Our results demonstrated that resulting increase of plasma renin concentration enhanced the consumption of renin substrate as shown by the fall of angiotensinogen levels measured by indirect method. In the rat, we observed the same drop of renin substrate during MK421 administration. The fall of angiotensinogen levels, measured by indirect method, was not in agreement with results of direct radioimmunoassay. This discrepancy can be explained by the accumulation of des-angiotensin I-angiotensinogen in plasma. These modifications are potentiated by sodium depletion.

Angiotensin I↗
PubMed1982

[Critical evaluation of the functional signs of arterial hypertension].

Influence of blood pressure levels on the prevalence of symptoms was studied in a group of 1771 untreated hypertensive patients referred to the Saint-Joseph Hypertension Clinic in Paris. Information on symptoms was obtained from a standardized physician-conducted interview during the patient's first visit at the Outpatient Clinic. The most frequent symptoms were headaches (40.5 p. 100), palpitations (28.5 p. 100), nocturia (20.4 p. 100) and dizziness (20.8 p. 100). Except for nocturia, symptom prevalence was higher in females than males. In males as well as in females, no correlation was found between blood pressure level and the presence of headaches, dizziness and palpitations when results were adjusted for age. In contrast, the relationship between two behavioural characteristics, anxiety and lack of regular physical activity, and symptom prevalence was more pronounced than the relationship with the blood pressure level itself. Moreover symptom prevalence differed significantly between the five permanent physicians of the Clinic; comparison of results obtained by physician conducted interview and self administered questionnaire indicated that difference between physicians were not due to difference in patient's characteristics but to differences in physician behaviour.

Adolescent↗
PubMed1982

[Incidence and fetal impact of hypertension in pregnancy: study of 2996 pregnancies].

To evaluate the incidence and the foetal effects of gestational hypertension, we studied 2 996 pregnancies with a single live birth in mothers selected on the basis of 1) a documented diastolic blood pressure (DBP) less than 90 mmHg before the 16th week of amenorrhea and 2) no history of hypertension or kidney disease. In 38,4% of the gravidas, the highest DBP during pregnancy was greater than or equal to 90 mmHg, and in 15,4% this level was reached twice or more. Gestational hypertension (two DBP readings greater than or equal to 90 mmHg) was more frequent in nullipara than in mothers with previous pregnancies (17,9 versus 12,4%, p less than 0,01) and its incidence tended to decrease with increasing maternal age. Irrespective of parity or maternal age, a significant increase in the percentage of small for gestational age infants was associated with increasing DBP levels: 3,2, 6,4 and 8,5% when the highest recorded DBP was less than 90 mmHg, equal to 90 mmHg (even at one single reading), or greater than or equal to 100 mmHg respectively (p less than 0,001). Very similar percentages were obtained in non-proteinuric pregnancies: 3,3, 6,5 and 7,8 respectively (p less than 0.001). Non-proteinuric gestational hypertension, even mild or transitory, is indicative of a high risk pregnancy and requires close medical supervision.

Blood Pressure↗