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Biomedical subjects

J Menard

Publications and source records attributed to J Menard.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

Synthesis and renin inhibitory properties of a new soluble pepstatin derivative.

A new pepstatin derivative, pepstatinyl arginine methyl ester hydrochloride (pepstatinyl-Arg-O-Me), was synthesized with the aim of increasing water solubility without altering capacity to inhibit the renin-angiotensinogen reaction. Pepstatinyl-Arg-O-Me was shown to inhibit in vitro the reaction between either rat or purified hog renin and the natural rat renin substrate. In a fluorimetric assay, this derivative competitively inhibited the reaction between purified hog renin and a synthetic N-acetyl-tetradecapeptide renin substrate with a Ki of the same order of magnitude as that of pepstatin. In urethaneanesthetized ganglion-blocked rats, binephrectomized 24 hr before the experiments, both the plasma reinin concentration and the rise in blood pressure following intravenous injection of hog renin were inhibited by pepstatinyl-Arg-O-Me disappeared within 60 min. Pepstatinyl-Arg-O-Me inhibited the 1.4 mumoles/kg. The in vivo inhibitory effect of 1.4 mumoles/kg of pepstatinyl-Arg-O-Me disappeared within 60 min. Pepstatinyl-Arg-Op-Me inhibited the reaction of endogenous and exogenous renin with plasma substrate both in vitro and in vivo.

Angiotensin II↗
PubMedDate not supplied

Dose dependency of captopril effects in severely hypertensive patients.

In a double-blind randomized study, the dose response to captopril was studied in 12 severely hypertensive patients whose blood pressure had been previously controlled by this converting enzyme inhibitor, either in association with a diuretic (seven patients), or with a diuretic and a beta-blocker (five patients). All patients received in random sequence 32.5, 75, and 150 mg/day of captopril in three divided doses. Significant correlations were revealed between the dose administered and the levels of arterial blood pressure, plasma renin, plasma aldosterone and plasma potassium. Under the conditions of this study, dose-response curves were obtained for concentrations of captopril between 0.5 and 4 mg/day/kg body weight.

Aldosterone↗
PubMedDate not supplied

Direct radioimmunoassay of human renin: comparison with renin activity in plasma and amniotic fluid.

Human plasma and amniotic liquid were activated by dialysis at pH 3.3. Then, renin before and after acidification was determined by two methods: enzymatic activity measurement, and direct radioimmunoassay. The identity between nonactivated and activated renin in plasma and amniotic fluid on the one hand, and pure renin on the other, was demonstrated by the dilution curves in radioimmunoassay. After acidification, mean plasma renin activity in 17 patients with high renin activity rose from 26.8 +/- 11.7 pmoles A I ml-1 h-1 to 67.9 +/- 29.3 pmoles A I ml-1 h-1, whereas the mean renin concentration tested by direct radioimmunoassay remained constant at 13.8 +/- 10.5 and 14.8 +/- 11.2 fmol/ml before and after acidification respectively. In amniotic fluid, renin activity increased from 9.7 to 227 pmoles angiotensin I/ml/h, but the renin concentration did not change. Direct radioimmunoassay of renin may therefore be considered as measuring total renin, regardless of its enzymatic activity. In 12 hypertensive patients undergoing bilateral renal-vein catheterization, the direct measurement of renin was very significantly correlated to the non-activated (r = 0.883) and activated renin values (r = 0.963).

Amniotic Fluid↗
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Role of angiotensinogen in blood pressure homeostasis.

The role of angiotensinogen in blood pressure control was assessed in normotensive rats by observing the changes resulting from inhibition by specific rat angiotensinogen antiserum. The antiserum decreased blood pressure in rats on normal sodium as well as sodium-free diets (respectively delta BP = -30 +/- 6 mm Hg and -42 +/- 8 mm Hg). In binephrectomized sodium-replete rats, administration of antiserum did not reduce blood pressure, whereas in sodium-depleted animals it slightly decreased blood pressure by 11 +/- 3 mm Hg. These results suggest that angiotensinogen participates in the regulation of blood pressure in normotensive rats, even in the sodium-replete state.

Angiotensinogen↗
PubMedDate not supplied

How much can blood pressure be lowered?

Whatever the therapeutic goal proposed for diastolic blood pressure in hypertensive patients, the actual results of treatment in various health care delivery systems throughout the world are not as good as generally assumed. In the two recent controlled therapeutic trials, 24.5% (Australian trial) and 29.9% (Hypertension Detection and Follow-up Program) of actively treated patients had diastolic blood pressure levels above 90 mm Hg. In three British hospital clinics, diastolic blood pressure was greater than 90 mm Hg in 69% of the treated patients after 6 months to 1 year of treatment. In our own clinic, the blood pressure of 947 hypertensive patients registered in the Artemis system (Paris) between 1976 to 1980 decreased after 2 years on medical treatment from 177/108 to 142/87 mm Hg. However 21.1% of the patients studied still had a diastolic blood pressure above 95 mm Hg. In the general population, the percentage of treated patients not attaining goal levels varies from 42.9% to 71%. Not only is it important to agree upon goals, but it is urgent to standardize methods for collecting and analyzing the results of antihypertensive treatments in various health care delivery systems, since high rates of therapeutic failures might be related to the physician's strategy, the patient's characteristics, the disease's particularities, and the limited efficacy and side-effects of presently available drugs.

Antihypertensive Agents↗
PubMedDate not supplied

Diagnosis and treatment of renin-secreting tumors. Report of three cases.

During the past 10 years, we have found renin-secreting renal juxtaglomerular cell tumors in three hypertensive patients (two women, one man, aged 22, 69, and 21 years, respectively). The major chemical and biological findings revealed the association of severe hypertension with hypokalemia and increased plasma renin activity and plasma aldosterone. The diagnosis of such tumors is difficult, and two of the three patients were followed up for four and five years respectively before undergoing surgery. The pharmacological blockade of the renin system by various agents (beta-blockers, angiotensin II antagonists, and captopril) and its effects on blood pressure and plasma renin activity proved to be unreliable. Renal venous catheterization for renin measurements failed to provide adequate localization of the tumor. Direct radioimmunoassay, however, showed the total plasma renin to be markedly elevated. In addition, renal arteriography showed an avascular area corresponding to the renin-secreting tumor in each of the three patients. All three patients were cured of hypertension and hypokalemia by excision of the tumor.

Adult↗
PubMedDate not supplied

Production and characterization of monoclonal antibodies to rat angiotensinogen.

Three stable monoclonal antibodies to rat angiotensinogen were obtained by fusing myeloma cells with spleen cells from Balb/c mice injected with pure rat angiotensinogen. They were screened by their binding to pure iodinated angiotensinogen and to insolubilized angiotensinogen in a solid phase assay. The titers of the three antibodies varied from 1/3500 to 1/35000, their dissociation constants from 2.5 X 10(-8) M to 3.8 X 10(-10) M, and the sensitivity of the assay ranged from 200 to 10 pmol of pure angiotensinogen. These monoclonal antibodies did not recognize either angiotensin peptides or angiotensinogen from other species, except for mouse angiotensinogen, which cross-reacted with the different antibodies from 0 to 25%. Rat cerebrospinal fluid angiotensinogen, plasma des-angiotensin I-angiotensinogen, and plasma angiotensinogen were equally recognized by these monoclonal antibodies. Contrary to what was observed for a polyclonal antiserum, the monoclonal antibodies failed to inhibit the renin-angiotensinogen reaction in vitro.

Angiotensinogen↗
PubMedDate not supplied

Nonproportional changes in plasma renin concentration, renal renin content, and rat renin messenger RNA.

The expression of the renin gene in rat kidneys was studied using mouse submaxillary gland renin complementary DNA. The length of rat renin messenger RNA (mRNA) was approximately 1600 nucleotides, similar to that of mouse submaxillary gland and kidney renin mRNA. Rat renin mRNA was quantified by a radiodensitometric complementary DNA hybridization assay. The effects of intense long-term stimulation and short-term inhibition of renin secretion on plasma renin concentration, renal renin concentration, and renin mRNA content were compared with those of controls. After 15 days of sodium depletion and captopril treatment, plasma renin concentration increased 46-fold, renal renin concentration only 1.5-fold, and renin mRNA content increased about threefold. Following a 1-hour infusion of angiotensin II in sodium-depleted and captopril-treated rats, plasma renin concentration decreased by 84% whereas no significant changes in either renal renin concentration or renin mRNA content were observed. These results show that sodium depletion and captopril treatment increase the level of renin gene transcription and renin biosynthesis. However, there are nonproportional changes in plasma renin levels, renal renin content, and its mRNA. These results suggest that newly synthesized renin is not stored in the kidney but is rapidly secreted into the blood. Short-term inhibition of plasma renin concentration by angiotensin II is most likely mediated by posttranslational mechanisms.

Angiotensin II↗
PubMedDate not supplied

[Proceedings: Role of endogenous and exogenous ACTH on aldosterone secretion (author's transl)].

The role of ACTH in the control of aldosterone secretion has been investigated in volunteers under a normal sodium diet. Endogenous ACTH suppression by dexamethasone (DXM) does not alter the plasma aldosterone (PA) response to 20 mg furosemide since identical PA increases are observed in control subjects and in subjects with DXM suppressed endogenous ACTH. The sodium depletion induced by furosemide during continuous ACTH infusion increases plasma renin activity but does not change PA.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

[Conn's syndrome].

Explore the source record for details and available documents.

Humans↗
PubMedDate not supplied

[Sensitive radioimmunoassay for plasma arginine vasopressin (author's transl)].

Using an ion exchange resin, a sensitive radioimmunoassay for plasma arginine vasopressin (AVP) was developed. This assay was characterized by the absence of blank values, an excellent recovery rate, great sensitivity (0.1 pg of AVP was significantly detected) and reproducibility. In 8 normal men, plasma AVP after overnight dehydration was 1.57 +/- 0.17 pg/ml and dropped to 0.58 +/- 0.11 pg/ml after 20 ml/kg oral water loading. Significant correlations between plasma AVP levels and plasma or urinary osmolality confirm the validity of this assay. In complete pituitary diabetes insipidus (n = 4) plasma AVP was undetectable whereas it was frankly increased in Schwartz-Bartter syndrome (3 to 33 pg/ml, n = 8).

Adult↗
PubMedDate not supplied

Use of a standardized personal medical record by patients with hypertension: a randomized controlled prospective trial.

It is widely believed that patients' compliance can be increased by persuading them to participate in their own care. We tested whether patients with hypertension could manage their own clinical records and whether their doing so would affect the quality of their care. Two hundred patients were randomly assigned to an intervention or a control group. Those in the intervention group were asked to complete a 10-page booklet containing a personal standardized medical record. All patients were scheduled for a follow-up appointment at the end of one year and were referred to their general practitioners for interim care. At the end of the follow-up period, the proportion of patients seen was comparable in the two groups. More of the patients in the intervention group than in the control group filled out a questionnaire as requested, and more added comments. Within the intervention group, the proportion of patients seen and the fall in systolic blood pressure were significantly higher among the 44 patients who had completed the personal record as requested than among the 57 who had not. Patients who completed the personal record also had fewer compliance problems.

Adult↗