Irene Gavras

Prediction of sustained antihypertensive efficacy of chronic captopril therapy: Relationships to immediate blood pressure response and control plasma renin activity

The blood pressure (BP) lowering effect of the orally active angiotensin converting enzyme inhibitor, captopril (SQ14225), was studied in 59 hypertensive patients maintained on a constant sodium intake. Within 2 hours of the first dose of captopril BP fell from 171/107 to a maximum low of 142/92 mm Hg (p less than 0.001), and after 4 to 8 days to treatment BP averaged 145/94 mm Hg (p less than 0.001). The magnitude of BP drop induced by captopril was significantly correlated to baseline plasma renin activity (PRA) both during the acute phase (r = -0.38, p less than 0.01) and after the 4 to 8-day interval (r = -0.33, p less than 0.01). Because of considerable scatter in individual data, renin profiling was not precisely predictive of the immediate or delayed BP response of separate patients. However, the BP levels achieved following the initial dose of captopril were closely correlated to BP measured after 4 to 8 days of therapy, and appeared to have greater predictive value than control PRA of the long-term efficacy of chronic captopril therapy despite marked BP changes occurring in some patients during the intermediate period. Because of these intermediate BP changes, addition of a diuretic to enhance antihypertensive effectiveness of angiotensin blockade should be restrained for several days after initiation of captopril therapy.

Safety and Efficacy of Chronic Therapy with Captopril in Hypertensive Patients: An Update

Abstract: Captopril, an orally active angiotensin‐converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long‐term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin‐angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.

A Comparative Study of the Effects of Oxprenolol Versus Propranolol in Essential Hypertension

LOWERING of high blood pressure is one action of /3-adrenoceptor blockade shared by most

CHRONIC SYMPATHETIC SUPPRESSION IN THE TREATMENT OF CHRONIC CONGESTIVE HEART FAILURE

antagonists. Since the first ff-adrenergic blocker proved clinically useful was propranolol, it has become the prototype to which other similar compounds are compared. Propranolol is a nonselective

Salt-induced hypertension in chronic renal failure: Evidence for a neurogenic mechanism

-adrenergic blocking agent, possessing affinity for both the /3, cardiac receptors and the

Calcium Antagonism Abolishes the Antipressor Action of Vasopressin (V1) Receptor Antagonism

2 extracardiac ones. It has no intrinsic /3-adrenergic agonistic effect but has some properties unrelated to /3-adrenergie activity, i.e., a cardiodepressant and a quinidine-like membrane stabilizing action. Its value as an antihypertensive agent is well established, although its exact mechanism of action remains a subject of debate. Oxprenolol is also a nonselective /3adrenoceptor blocker with a quinidinelike effect, but with less pronounced negative inotropic action, and, unlike propranolol, it has considerable intrinsic

Acute cardiovascular effects of two central phenylethanolamine-N-methyl-transferase inhibitors in unanesthetized desoxycorticosterone-salt hypertensive rats

Previous short-term studies demonstrated that treatment with clonidine produced significant hemodynamic improvement in patients with congestive heart failure (CHF). In this study we followed 12 CHF patients (10 M, 2 F age 63+/-11, 10 with ischemic cardiomyopathy and 2 with dilated cardiomyopathy) treated with 0.15 or 0.075 mg oral clonidine twice daily for 13+/-5 months (range 6-23). with functional evaluation at baseline, 6 weeks and 6 months. There was suppression of circulating catecholamines, associated with significant ameliorations in NYHA class, in duration of exercise tolerance (from 246+/-68 sec to 362+/-30 and 459+/-70 sec, respectively p < 0.02), in ejection fraction (from 32+/-7% to 35+/-5 and 39+/-7% p < 0.04) and in left ventricular enlargement as assessed echocardiographically. There were also improvements in a number of electrophysiologic parameters calculated by computerized analysis of ambulatory ECG tapes, such as heart rate variability, indicating diminished propensity to malignant arrhythmias, as confirmed by decreases in the numbers of isolated premature ventricular contractions, couplets and episodes of non-sustained ventricular tachycardia. The data suggest that chronic central sympathetic suppression with clonidine in CHF results in significant functional amelioration and improved electrophysiologic stability.

The Renin-Angiotensin System and the Heart

Abstract We investigated the possibility that blood pressure elevation induced by salt excess may be secondary to a neurogenic mechanism. The compound SK&F 64139 (50 mg/kg) known to inhibit central and peripheral phenylethanolamine N-methytransferase (PNMT) the enzyme necessary for the conversion of norepinephrine to epinephrine, was given by oral gavage to two groups of subtotally nephrectomized rats maintained for five days on either a high salt (HS) or low salt (LS) diet respectively. Blood urea nitrogen (BUN) and hematocrit were not different between the two groups, while body weight and serum Na were significantly higher in the HS animals. Baseline mean blood pressure (BP) was higher in the HS animals (HS 154 ± 4.7 vs LS 121 ± 3.7 mmHg, p

Hypertension in the elderly: pathophysiology of aging of the cardiovascular system

Previous studies demonstrate that vasopressin (V1) receptor antagonism lowers arterial pressure in blacks. This action of V1 receptor blockade may be mediated through various mechanisms including changes in intracellular calcium fluxes. This study was undertaken to test the hypothesis that inhibition of calcium entry may attenuate the reduction in arterial pressure observed with V1 receptor blockade. Sixteen hypertensive patients, 8 whites and 8 blacks, were examined. Each had their antihypertensive therapy stopped for 1 week. Following three baseline blood pressure measurements, all patients were given an intravenous bolus injection of a V1 receptor antagonist. Blood pressure was monitored every 10 min for a period of 3 h. Subjects were then randomized to either 0.2 mg clonidine twice daily or 300 mg diltiazem CD daily for a period of 3 days and the previous experiments repeated. Patients were then crossed over to the other drug for an additional 3 days and the experiments repeated. There was a significant reduction from baseline in the mean arterial pressure among blacks but not whites (-11 +/- 3 delta mm Hg blacks versus -1 +/- 2 delta mm Hg whites, P < .01). In the presence of clonidine, there were similar reductions in arterial pressure in both groups (P = .026) with a further reduction following V1 receptor blockade only in the blacks (-7 +/- 3 delta mm Hg blacks versus 6 +/- 2 delta mm Hg whites; P < .001). Conversely, in the presence of diltiazem CD, there were no further reductions in arterial pressure in either group following the V1 receptor antagonist. We conclude that calcium channel blockade abolishes the blood pressure lowering response of V1 receptor blockade in blacks.

Hypertension, Vasopressors, and Susceptibility to Vascular Injury: Experimental and Clinical Studies

SKF 64139, an inhibitor of phenylethanolamine-N-methyltransferase (PNMT), has a marked hypotensive effect in models of sodium-dependent hypertension. The mechanism of this effect is obscure, the compound having in addition alpha-adrenoceptor blocking properties. We compared the acute effects of SKF 64139 with those of LY 134046, another PNMT inhibitor with minimal alpha-blocking capacity, in desoxycorticosterone-salt hypertensive rats. The former agent produced profound hypotension whereas the latter caused only bradycardia. Both induced a similar pronounced suppression of PNMT activity in the C1 and C2 region of the medulla oblongata. These results suggest that the alpha-adrenergic effect rather than PNMT inhibition accounts for the acute lowering of blood pressure in this model.