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Biomedical subjects

H Gavras

Publications and source records attributed to H Gavras.

At least 163 records · Page 9Linked to original sources
PubMed1986

A multicenter trial of enalapril in the treatment of essential hypertension.

The therapeutic profile of enalapril in mild to moderate uncomplicated essential hypertension was assessed in 265 patients who participated in a multicenter, open-label, prospective study lasting eight weeks. There were 54 younger (aged 39 years or less), 136 middle-aged (40 to 59 years), and 75 older patients (60 years or over). Monotherapy with enalapril in a single daily dosage regimen ranging between 5 and 40 mg resulted in normotension (in the sitting position) in 73% of the younger, 50% of the middle-aged, and 56% of the older patients. Normotension was achieved with 5 mg/day of enalapril in 41%, 18%, and 37% of the subgroups, respectively. Both systolic and diastolic pressures at the end of eight weeks of treatment were significantly lower (P less than 0.01) in the younger patients than in the other two age groups. White patients had significantly greater (P less than 0.001) response of both systolic and diastolic blood pressures than did black patients and required significantly smaller (P less than 0.01) average daily dosages of enalapril (14 mg versus 22 mg, respectively). The overall incidence of side effects was 14% among all 276 patients enrolled in the study. Most were mild and transient, but six patients discontinued enalapril during the first week of therapy because of side effects. There were no cases of rash, dysgeusia, hematological disorders, or deterioration in renal function, but there were two cases of pruritus, one of glossitis associated with an upper respiratory infection, and three of dry cough or wheezing. Angioedema was not observed. Monotherapy with enalapril, usually in a single daily dose of 10 to 20 mg, was effective in inducing normotension in approximately half of the middle-aged and older hypertensive individuals and in nearly three fourths of those below age 40. In this study it was generally well tolerated, with a relatively small incidence of side effects.

Adult↗
PubMed1985

alpha-Adrenoceptor agonists applied in the area of the nucleus tractus solitarii in the rat: effect of anesthesia on cardiovascular responses.

We investigated the blood pressure and heart rate responses to unilateral local application of norepinephrine or clonidine in the area of the nucleus tractus solitarii (NTS) of conscious rats and rats anesthetized by 3 general anesthetics commonly used in cardiovascular research. In the conscious state, microinjection of either substance produced an immediate, sharp increase in blood pressure and decrease in heart rate with a gradual return to baseline over a period of more than 30 min. However, light ether anesthesia, nembutal, or urethane drastically reduced, abolished or even reversed the pressor effect of local microinjection of the same substance. Our results suggest that in conscious rats, the initial effect of alpha agonists in the NTS area is to modulate baroreceptor reflexes towards higher blood pressure levels and that general anesthesia may significantly alter or mask the cardiovascular responses to various experimental manipulations.

Adrenergic alpha-Agonists↗
PubMed1985

Hypertensive response to saline microinjection in the area of the nucleus tractus solitarii of the rat.

We investigated the blood pressure response elicited by microinjection of various hypertonic solutions into the area of the nucleus tractus solitarii (NTS) of the brainstem, an area rich in catecholaminergic neurons. Equiosmolar solutions of NaCl, dextrose, LiCl and KCl were employed. NaCl produced a prolonged blood pressure rise; LiCl and normal saline produced a similar rise of short duration; and KCl produced epileptic-type seizures with postictal hypertension. Dextrose had no effect and neither had NaCl microinjection in areas relatively distant from the NTS. The rise in blood pressure was not reversed by a vasopressin antagonist injected systemically, but was totally abolished by systemic alpha-adrenergic blockade with phentolamine. These findings suggest that sodium can cause hypertension by direct stimulation of the central sympathetic nervous system without participation of peripheral mechanisms such as fluid volume expansion or alteration of the vascular wall.

Animals↗
PubMed1985

Nifedipine in the treatment of essential hypertension.

The antihypertensive efficacy of nifedipine as a second-step drug in 24 patients, uncontrolled by a diuretic alone, was studied according to a double-blind placebo-controlled protocol. A significant blood pressure lowering was observed in nine out of 12 patients receiving the active drug and four out of 12 receiving placebo. Average mean blood pressure decreased by 13 +/- 1 mm Hg in the active drug group versus 5 +/- 3 mm Hg in the placebo group (P less than .02). There were no consistent changes or significant differences in heart rate or in the levels of plasma renin activity and plasma catecholamines between the two groups. In conclusion, nifedipine appears to be a safe and effective antihypertensive agent when used in conjunction with a diuretic for the treatment of moderately severe hypertension.

Blood Pressure↗
PubMed1985

The contribution of the renin-angiotensin system to limb vasoregulation in patients with heart failure: observations during orthostasis and alpha-adrenergic blockade.

1. In patients with congestive heart failure, both the sympathetic nervous system and renin-angiotensin system are often stimulated. In order to assess the contribution of the renin-angiotensin system to limb vascular resistance, the forearm haemodynamic response to captopril was studied in 13 patients with heart failure. 2. Seven subjects were studied while supine and during 60 degrees head-up tilt. To eliminate alpha-adrenergic effects, six additional patients with heart failure were pretreated with intra-arterial phentolamine and then given captopril. Venous occlusion plethysmography was used to determine forearm blood flow and forearm vascular resistance. 3. Tilt did not significantly increase pretreatment plasma renin activity or plasma noradrenaline concentration, nor did it decrease forearm blood flow. Furthermore, captopril did not alter forearm vascular resistance during supine or upright posture. During the phentolamine infusion, however, captopril reduced forearm vascular resistance by 19% (P < 0.05). 4. Despite increased plasma renin activity, captopril did not cause forearm vasodilatation during supine or upright posture in these patients with heart failure. When the contribution of the sympathetic nervous system was eliminated, captopril decreased forearm vascular resistance. Therefore, in patients with congestive heart failure, the sympathetic nervous system is important in limb vasoregulation, and the contribution of the renin-angiotensin system is apparent only after alpha-adrenergic blockade.

Adrenergic alpha-Antagonists↗
PubMed1985

Sodium chloride-induced partial inhibition in vivo of alpha 2-adrenoceptor agonist function.

Recent research has demonstrated that sodium diminishes the affinity of alpha 2-adrenoceptors for agonists in vitro. Clonidine, a highly specific agonist for alpha 2-receptors, has a transient hypertensive effect when administered parenterally. We studied in conscious anephric Wistar rats the effect of equimolar saline or mannitol solutions on the hypertensive response to clonidine administered subcutaneously in doses of 10, 100 and 1000 micrograms/kg body weight. Prior saline infusion reduced the hypertensive response to the two higher doses of clonidine by 65 and 70%, and displaced the slope of the dose-response curve downwards, but mannitol had no such effect. Pre-treatment with the alpha 2-antagonist yohimbine abolished the differences in clonidine-induced pressor response between saline-treated, mannitol-treated and control rats. On the contrary, after pre-treatment with the alpha 1-antagonist prazosin, the pressor action of clonidine was significantly reduced in the saline-infused rats compared to the other two groups. Thus the saline-induced blunting of the pressor response elicited by clonidine could be negated by prior alpha 2- but not alpha 1-blockade, indicating that sodium interfered with the stimulation of post-synaptic vascular alpha 2-adrenoceptors. These findings indicate that loading with sodium chloride attenuates the alpha 2-adrenoceptor function in vivo. Based on this, we suggest that the mechanism by which sodium excess causes a rise in blood pressure involves modification of the alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1985

Cardiovascular effects of dobutamine and converting enzyme inhibition in rats with diabetic ketoacidosis.

We investigated cardiac and peripheral hemodynamics in rats with streptozotocin-induced diabetes mellitus in comparison to normal controls. Diabetic rats showed a significantly decreased cardiac output and heart rate, with unchanged mean blood pressures. Regional blood flows were unchanged except for renal blood flow which was significantly lower. The low output state associated with diabetes was reversed by angiotensin converting enzyme inhibition with MK-422, but not with dobutamine, although both agents caused similar reduction in peripheral vascular resistance. However, despite improved left ventricular performance, renal perfusion did not improve after MK-422.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Renal revascularization in the azotemic hypertensive patient resistant to therapy.

We undertook this study to assess the frequency of renovascular hypertension in patients with azotemia and hypertension refractory to drug therapy and to determine the effects of renal revascularization on blood pressure and renal function in these subjects. Thirty-nine of 106 consecutive patients admitted for diagnostic evaluation of severe hypertension proved to have renovascular hypertension. Of 21 hypertensive patients with renal insufficiency, 10 appeared to have renovascular hypertension with either bilateral atherosclerotic renovascular disease or unilateral renal arterial stenosis in a solitary functioning kidney. Medical therapy in the hospital often induced further deterioration of renal function despite enhanced blood-pressure control. However, surgical revascularization or percutaneous transluminal angioplasty produced improvement or stabilization of renal function and control of blood pressure in all patients with azotemia who were treated in this manner, despite longstanding hypertension. The benefits of therapy have persisted for 10 to 42 months of follow-up. These studies indicate that refractory hypertension in association with renal insufficiency is a relatively common clinical presentation for renovascular hypertension and bilateral renal-artery disease. Diagnostic evaluation and consideration of renal revascularization appear warranted in such patients, both for the control of the hypertension and for improvement in renal function.

Aged↗
PubMed1984

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

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.

Animals↗
PubMed1984

Cardiovascular responses in the diabetic rat.

Cardiac and regional haemodynamics have been studied in 12- and 15-week-old streptozotocin-diabetic rats and in non-diabetic controls. Reduced cardiac output has been found in the 15-week-old diabetic rats (64 +/- 13 ml/min, mean +/- S.D.), while 12-week-old diabetic rats expressed normal values (104 +/- 25 ml/min, mean +/- S.D.). Renal blood flows of 12- and 15-week-old diabetic rats (3.4 +/- 1 ml/min . g and 3.7 +/- 1 ml/min . g, mean +/-S.D. respectively) were similarly decreased, when compared to those of non-diabetic rats (5.47 +/- 1 ml/min . g). This finding could be only partly attributed to the increased plasma renin activity of the 12- and 15-week-old diabetic rats (16.6 +/- 6 ng/ml . h and 19.3 +/- 4 ng/ml . h respectively), which were higher than normal (4 +/- 1 ng/ml . h). Otherwise the circulations of the brain, heart, gastrointestinal and musculocutaneous systems were similar in the diabetic and non-diabetic rats. In conclusion, while cardiac output was decreased only in the 15-week-old diabetic rats, renal perfusion was altered at an earlier stage of the diabetic process.

Animals↗
PubMed1984

Does vasopressin sustain blood pressure of normally hydrated healthy volunteers?

The inhibitor of the pressor effect of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP, at a dose of 5 micrograms/kg iv was shown in four healthy volunteers to antagonize the blood pressure, heart rate, and skin blood flow response to a lysine vasopressin infusion of 1 mIU X kg-1 X min-1. The inhibition lasted for more than 2 h. When the same dose of the vasopressin antagonist was administered to 10 healthy normally hydrated volunteers with their renin system intact or acutely blocked by 25 mg of captopril po, none of the above parameters changed. It is concluded that circulating vasopressin, even in the face of a blocked renin-angiotensin system, does not actively contribute to maintenance of cardiovascular homeostasis.

Adult↗
PubMed1984

Effect of renin-angiotensin system on limb circulation in normal subjects.

It is not known whether the renin-angiotensin-aldosterone (RAA) system contributes to the regulation of the limb circulation in normal human beings. Accordingly, the effect of the angiotensin converting-enzyme inhibitor, captopril, on forearm vascular resistance (FVR) and forearm venous volume (FVV) was studied in nine normal subjects during states of both sodium loading and sodium depletion. All subjects were studied in the supine position and during 60 degrees head-up tilt. By analysis of variance, the combined intervention of sodium depletion and converting-enzyme inhibition was responsible for a decrease in both FVR and mean blood pressure (BP). In sodium-depleted subjects, converting-enzyme inhibition decreased supine mean BP 7.0% and supine FVR 22.8% but did not change FVV. Neither the fall in BP nor the fall in FVR, however, was significantly augmented by tilting from a supine to upright posture. In sodium-loaded subjects, captopril did not alter BP, FVR, or FVV in recumbent or upright positions. Therefore, the RAA system contributes to the maintenance of blood pressure and limb vascular resistance only in sodium-depleted subjects. Limb venous capacitance in normal subjects is not regulated by the RAA system.

Adult↗
PubMed1984

Vasopressin response to hyperosmotic stimulus: blood pressure effect in normal subjects and patients with impaired sympathetic system.

We have investigated the interaction of plasma vasopressin and plasma catecholamines in quadriplegic patients (with severed sympathetic tracts) and compared them to others with intact sympathetic system following I.V. administration of a hyperosmolar radiocontrast agent during a routine diagnostic pyelography. Baseline systolic and diastolic pressure as well as plasma norepinephrine were significantly lower in the quadriplegic subjects. At 5 minutes after administration of the hyperosmolar solution, systolic and diastolic pressure as well as plasma vasopressin rose in the quadriplegic subjects but not in normal subjects despite a significant and equal rise in serum osmolality occurring in both groups. These results demonstrate that an interaction between the two systems exists in humans: an intact sympathetic nervous system attenuates the vasopressin response to hyperosmolar stimuli and in its absence vasopressin may function as a pressor agent.

Adult↗
PubMed1984

Regional blood flows and cardiac hemodynamics in renovascular and mineralocorticoid hypertensive rats.

Regional blood flows and cardiac hemodynamics were studied in 3 models of hypertensive rats: one-kidney DOC-saline, one-kidney, one-clip and two-kidney, one-clip hypertension and in normotensive control rats. All hypertensive models were characterized by increased peripheral vascular resistance and normal cardiac output. Coronary and cerebral blood flows varied among the hypertensive models but did not significantly differ from the normotensive rats. However, coronary blood flow of one-kidney, one-clip rats (8.4 +/- 1.3 ml X min-1 X g-1) was significantly higher than that of the two-kidney one-clip rats (6.5 +/- 1.2 ml X min.-1 X g-1, P less than 0.05). Cerebral blood flow of DOC-saline rats was lower than that of two-kidney one-clip or one-kidney one-clip renovascular rats. Renal blood flows of the unclipped kidney of two-kidney renovascular rats (3.77 +/- 0.85 ml X min-1 X g-1) and DOC-saline rats (2.95 +/- 0.83 ml X min-1 X g-1) were significantly lower than those of normotensive rats (5.92 +/- 1.16 ml X min-1 X g-1, P less than 0.05). In conclusion, although vascular resistance becomes elevated in all models of experimental hypertension, regional vascular resistance and blood flow distribution may differ depending on the vasoconstrictor mechanisms that participate in each model.

Animals↗
PubMed1984

Evidence for dopaminergic regulation of vasopressin release in the anephric rat.

Arginine vasopressin (AVP) release elicited by osmotic stimuli induces variable hypertensive responses. In normotensive anephric rats, a significantly greater blood pressure response was elicited by hypertonic saline than by mannitol infusion, and was further enhanced by previous dopaminergic receptor blockade. Plasma levels of AVP were significantly more elevated after saline than after mannitol despite more pronounced elevation of plasma osmolality in the latter animals, and were the highest in dopaminergically blocked animals. These findings indicate that dopamine exerts an inhibitory effect on the release of AVP.

Animals↗