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Biomedical subjects

H Gavras

Publications and source records attributed to H Gavras.

At least 235 records · Page 13Linked to original sources
PubMed1979

Orally active angiotensin-converting enzyme inhibitor (SO 14,225) as a treatment for essential hypertension.

1 Captopril (SQ14,225), an orally active inhibitor of angiotensin-converting enzyme, was administered to nine patients with essential hypertension. Plasma renin activity (PRA) was low in four, 'normal' in three and high in two patients. 2 In the hospital, captopril alone induced a significant drop in BP from 165 +/- 6/106 +/- 2 to 140 +/- 5/90 +/- 1 mmHb (P less than 0.001). PRA increased concomitantly (P less than 0.05), whereas plasma-converting enzyme activity (P less than 0.005) and plasma aldosterone (P less than 0.05) were reduced. 3 Six patients underwent chronic ambulatory therapy with captopril for a mean of 16 +/- 3 weeks. After discharge from the hospital, BP remained normalized but in five out of six patients this required additional diuretic therapy. 4 The results suggest that captopril alone or combined with diuretic therapy provides a new, efficient and well tolerated tool to treat patients with essential hypertension independently of their PRA level. It may turn out to be more effective in lowering BP than beta-adrenoceptor-blocking agents.

Adult↗
PubMed1979

Conditioning effects of chronic infusions of dobutamine. Comparison with exercise training.

We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 mug/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10 degrees incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning. To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups. Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning.

Animals↗
PubMed1979

Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients.

The antihypertensive effect of the orally active angiotensin-converting enzyme inhibitor captopril (SQ 14225) was assessed in 22 hypertensive patients of whom 17 were followed for periods ranging from 1 to 7 months. Of these, eight had essential hypertension, eight had renovascular hypertension, and six had hypertension associated with chronic renal failure. Blood pressure decreased markedly in all patients, including those with low renin levels. Nevertheless, the magnitude of blood pressure reduction correlated with the base-line plasma renin activity (r = 0.58, P less than 0.01). Increasing the dose of captopril from 25 to 200 mg did not enhance the amplitude of the antihypertensive effect but did increase its duration. Patients' blood pressure remained well controlled and free of side-effects with a maximal daily dose of up to 200 mg by mouth twice daily. Despite the blood pressure reduction, sodium excretion tended to increase, probably because of reduced aldosterone secretion. There was no evidence of orthostatic hypotension, and no escape from the antihypertensive effect was observed. These results indicate that chronic inhibition of the angiotensin-converting enzyme with an orally active compound offers a new, efficient, and well-tolerated approach to the treatment of hypertension.

Adult↗
PubMed1979

Converting enzyme inhibition in hypertensive emergencies.

The diagnostic and therapeutic value of the angiotensin converting enzyme inhibitor teprotide (SQ 20881) was assessed in 18 patients with hypertensive emergencies. Mean blood pressure fell 31 +/- 18 mm Hg in the 10 subjects who responded to 1 mg/kg body weight administered intravenously, whereas it fell 5 +/- 3 mm Hg in the eight nonresponders. In patients who had received no previous drug treatment, log baseline plasma renin activity and change in mean blood pressure after SQ 20881 correlated significantly (r = 0.651, P less than 0.05). After acute therapy with SQ 20881, the patients who had a satisfactory response to the drug were treated with propranolol and a relatively normal sodium intake (88 meq/day). Nonresponders were treated with diuretics and sodium restriction (10 meq/day), and intermediate responders were given combination therapy. Mean blood pressure responded favorably within 24 h to the chosen regimen for each group from 152 +/- 47 to 102 +/- 31 mm Hg. SQ 20881 allows prompt evaluation of the role of renin in hypertensive emergencies and permits early choice of appropriate therapy based on the prevailing mechanism.

Adult↗
PubMed1979

Captopril and salt subtraction to treat "uncontrollable" hypertension in haemodialysis patients.

Eight patients on chronic haemodialysis for six months to 7 years with hypertension resistant to ultrafiltration and antihypertensive therapy, received Captopril (SQ 14, 225) an orally active inhibitor of converting enzyme. With this therapy, blood pressure was controlled in the 4 patients with the highest plasma renin activity. In the other 4, this treatment had to be supplemented with "isovolumetric salt subtraction", i.e. following conventional dialysis, 1-2 litres of ultrafiltrate were replaced by an equal volume of 5% glucose. The slight hyponatraemia induced by this procedure (plasma sodium 128mmol/L) was well tolerated. This procedure allows the removal of an excess of body sodium and seems to be effective even when conventional ultrafiltration during dialysis has failed. Administration of Captopril either alone or combined with "isovolumetric salt subtraction" induced good control of blood pressure in all 8 patients.

Adolescent↗
PubMed1979

Antihypertensive action of beta-adrenoceptor blockade and the renin-angiotensin system.

1 The regulation of renin secretion is mediated by way of adrenoceptors. The role of alpha-adrenoceptors remains controversial, whereas it is generally accepted that activation of beta-adrenoceptors stimulates renin and their blockade suppresses renin. 2 Although experimental renin regulation appears to be a beta 2-receptor function, clinical studies suggest that in man it is a beta 1 effect. 3 beta-Adrenoceptor-blocking agents are effective antihypertensive agents, but have variable effects on renin secretion; this variability may be attributable to different degrees of instrinsic partial beta-agonistic activity and/or different receptor or organ selectivity of various compounds. 4 Antihypertensive effectiveness seems unrelated in magnitude or timing to the baseline levels or the changes of plasma renin activity for the majority of beta-adrenoceptor-blocking drugs.

Adrenergic beta-Antagonists↗
PubMed1978

[Long-term minoxidil therapy: renin, aldosterone, noradrenaline and the need for beta blockers].

Minoxidil-induced sequential changes in plasma renin activity, urinary aldosterone and norepinephrine excretion were assessed in 11 patients with severe hypertension receiving propranolol or oxprenolol, chlorthalidone and spironolactone. Blood pressure with this treatment alone averaged 175 +/- 7/114+/-4 mm Hg (mean +/- SEM). Addition of minoxidil in a dose of 5 to 35 mg/day (mean 16 mg/day) reduced blood pressure within one week to 125+/-5/87+/-3 mm Hg. Plasma renin, urinary aldosterone and norepinephrine increased two- to threefold initially, but returned to baseline within two weeks and remained unchanged during a mean follow-up of 6.8 months. In 6 patients beta-blocking drugs were then progressively reduced and withdrawn without adverse effects, though blood pressure and heart rate increased slightly in 5 patients who required readministration of minimal doses of beta-blockers. Neither renin nor urinary aldosterone or norepinephrine excretion changed significantly after discontinuation of beta-blockade. Thus, the stimulating effect of minoxidil on renin, aldosterone and norepinephrine secretion lasts less than 3 weeks. With long-term minoxidil treatment the need for beta-blockade is markedly reduced, and these drugs may even become unnecessary in some patients.

Adult↗
PubMed1978

Peptidyl dipeptidase in rabbit brain microvessels.

The activity of peptidyl dipeptidase (peptidyldipeptide hydrolase, EC 3.4.15.1), also known as angiotensin-converting enzyme, was studied in small blood vessel preparations isolated from rabbit brain. The vascular preparation contained arterioles and capillaries and was essentially free of extravascular material. Enzymatic activity was demonstrated in microvessel homogenates using both hippuryl-histidyl-leucine and tritium-labeled angiotensin I as substrates. Activity in the microvessels was dependent on the presence of chloride ion and was sensitive to inhibition by converting enzyme inhibitors previously shown to be effective in both vivo and in vitro. Specific activity in the micro-vessels was approximately 20 times that in homogenates of brain, and was almost 60% of that found in rat lung homogenates. The data were consistent with an endothelial localication for peptidyl dipeptidase in the cerebral vasculature and supports the proposal that this enzyme has a physiological role in extrapulmonary vascular beds.

Animals↗
PubMed1978

Innappropriate renin secretion unmasked by captopril (SQ 14 225) in hypertension of chronic renal failure.

Captopril (SQ 14 225), an orally active inhibitor of angiotensin-converting enzyme, was given to 7 hypertensive patients with chronic renal failure whose plasma-creatinine ranged from 1.5--7.4 mg/dl; whose plasma-renin activity was normal; whose hypertension was not controlled by previous therapy consisting in 5 patients of three or more antihypertensive drugs; and whose blood-pressures averaged 176/111 +/- 11/3 mm Hg. Inhibition of converting enzyme by oral captopril, 200 mg twice daily, reduced blood-pressure to 156/100 +/- 9/5 mm Hg. 5 patients needed additional treatment by frusemide 40--250 mg/day orally. With this combined regimen the blood-pressure of all patients averaged 126/85 +/- 4/3 mm Hg after 8 +/- 2 weeks of captopril. The drug was well tolerated. These results suggest that inhibition of angiotensin-converting enzyme with or without sodium depletion is an efficient treatment for hypertension associated with chronic renal failure. It appears that although renin levels in patients with this condition may be "normal", they are inappropriate in relation to the subtle degree of sodium retention that occurs with this disorder.

Administration, Oral↗
PubMed1978

Need for beta-blockade in hypertension reduced with long-term minoxidil.

Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients.

Adrenergic beta-Antagonists↗
PubMed1978

Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man.

We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.

Administration, Oral↗
PubMed1978

Mechanism of blood pressure reduction by teprotide (SQ 20881) in rats.

The mechanism by which the angiotensin converting enzyme inhibitor, teprotide (SQ 20881), lowers blood pressure was assessed in anesthetized normotensive and spontaneously hypertensive (SHR) rats. Teprotide always was administered at a maximally effective dose of 1 mg/kg. In six normal Wistar rats, teprotide lowered blood pressure only after sodium depletion, an effect which was abolished by bilateral nephrectomy. Saralasin infusion (5 microgram/kg/min) into salt-depleted normal rats induced a blood pressure effect similar to that of teprotide. When administered in addition to saralasin infusion, teprotide did not reduce blood pressure further in normal rats or in SHR. When blood pressure of normal rats was raised by angiotensin II infusion (200 ng/kg/min), teprotide did not affect the induced blood pressure increase. In contrast, the pressure rise induced by angiotensin I infusion (230 ng/kg/min) was reversed by saralasin, but again concomitant administration of teprotide did not induce further blood pressure reduction. Thus, under the particular conditions of the present study, teprotide did not appear to exert its hypotensive effect by any mechanism other than inhibition of the renin-angiotensin system. Furthermore, given at a maximally effective dose to the rat, it produced no greater vasodepressor effect than did saralasin.

Angiotensin I↗
PubMed1978

Relationship of basal plasma noradrenaline to blood pressure, age, sex, plasma renin activity and plasma volume in essential hypertension.

1. The relationship of basal plasma noradrenaline to blood pressure, age, sex, urinary sodium excretion, and plasma volume has been examined in 117 untreated ambulatory patients with essential hypertension. 2. No significant correlations between basal plasma noradrenaline and either age or sex were apparent in the total group of essential hypertensive patients. In addition, no significant correlations were observed between plasma noradrenaline and 24 h urinary sodium excretion. 3. Basal plasma noradrenaline concentration was significantly higher in high renin essential hypertensive subjects compared with those with normal or low plasma renin activity. 4. Plasma noradrenaline was reduced significantly in relatively young patients with low renin essential hypertension, but appeared to be normal in other low renin subjects. 5. Basal plasma noradrenaline correlated significantly with blood pressure in patients with normal or low renin essential hypertension but the relationships were only significant in male patients. 6. No significant relationship between basal plasma noradrenaline and either blood pressure or plasma volume could be demonstrated in this population of essential hypertensive patients.

Age Factors↗
PubMed1978

Redistribution of regional blood flow after administration of saralasin in salt-depleted dogs.

1. Salt depletion was produced in five dogs by a low salt diet and daily administration of frusemide for 5 days; a control group of five dogs was placed on the same diet, to which 2.5 g of sodium chloride was added. 2. Saralasin infusion (0.5 microgram min-1 kg-1) reduced mean aortic blood pressure and total peripheral vascular resistance and increased cardiac output in salt-depleted dogs, but did not affect the heart rate and left ventricular dP/dt. 3. Saralasin infusion increased mean aortic blood pressure slightly in normal dogs; other systemic haemodynamic parameters did not change significantly. 4. Saralasin decreased hepatic arterial flow in both normal and salt-depleted dogs, but increased blood flow to left ventricle and kidneys only in salt-depleted dogs. 5. These results suggest that saralasin exerts a partial agonist effect in normal dogs to increase arterial blood pressure, but causes a depressor response during salt depletion because it reverses the vasoconstrictor effect of angiotensin II, particularly on the renal and coronary circulations.

Angiotensin II↗