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H Gavras

Publications and source records attributed to H Gavras.

At least 181 records · Page 10Linked to original sources
PubMed1983

Systemic and regional hemodynamic effects of propranolol in intact and anephric rats.

We studied the changes in systemic and regional hemodynamics (using the radioactive microsphere technique) and catecholamine levels produced by propranolol in conscious semi-restrained intact or nephrectomized rats. Blood pressure increased by 17 +/- 2 and 32 +/- 2 mmHg in intact and anephric rats respectively, total peripheral vascular resistance by 61.5% and 176.5%, heart rate decreased by 23% and 35% respectively, cardiac index decreased by 35% and 57%, and stroke volume index by 14% and 30%. All changes were significantly more pronounced in anephric rats (p less than 0.05). Baseline norepinephrine, epinephrine, and dopamine were significantly higher in anephric versus intact animals and did not change significantly after B-blockade except for norepinephrine of the anephric rats which decreased. After B-blockade regional blood flows in most organs (including coronary flow) decreased in proportion to the diminished cardiac index except for brain flow which decreased by only 12% in intact and 25% in anephric animals. Local vascular resistances increased concomitantly and these changes were far more pronounced in the absence of kidneys. Thus, anephric state exacerbates all systemic and regional hemodynamic alterations caused by B-blockade in the rat.

Animals↗
PubMed1983

Captopril and enalapril.

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure.

The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril and teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 +/- 240 to 1,715 +/- 170 dynes . s . cm-5 (p less than 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 +/- 8 to 86 +/- 5 mm Hg, p less than 0.001) and left ventricular filling pressure (30 +/- 2 to 21 +/- 2 mm Hg, p less than 0.001). Coronary sinus thermodilution blood flow paralleled perfusion pressure but did not significantly vary overall (160 +/- 20 to 133 +/- 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 +/- 8.8 to 41.3 +/- 7.9 g l m/m2, p less than 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 +/- 1.0 to 10.4 +/- 1.0 ml/10 ml, NS) or calculated myocardial oxygen consumption (16.4 +/- 1.9 to 13.9 /- 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 +/- 703 to 7,087 +/- 514 beats . mm Hg, p less than 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 +/- 3 to 26 +/- 6, p less than 0.05), reflecting greater left ventricular work without increased oxygen demand. Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.

Aged↗
PubMed1982

The effect of angiotensin converting enzyme inhibition of coronary blood flow and hemodynamics in patients without coronary artery disease.

We examined the role of the renin-angiotensin system in the regulation of systemic and coronary vascular tone by studying the effect of converting enzyme inhibition by teprotide on systemic and coronary hemodynamic parameters in 14 normal patients undergoing routine cardiac catheterization. Serial hemodynamic measurements were made before and up to 30 minutes after 1 mg/kg of intravenous teprotide. A significant rise in cardiac index and stroke volume index occurred with a fall in systemic vascular resistance. The increase in cardiac index was related to the level of resting plasma renin activity. Blood pressure, pulmonary artery and left ventricular end-diastolic pressures remained unchanged. Coronary sinus thermodilution blood flow also showed no significant change; however, some patients demonstrated dramatic increase in flow. The change in blood flow was highly correlated with the resting plasma renin activity (r = 0.939 P less than 0.001). The change in coronary vascular resistance and myocardial oxygen consumption were likewise related to the resting plasma renin level. Converting enzyme inhibition produces significant systemic hemodynamic changes in normal patients which implies that the renin-angiotensin system is important in normal cardiovascular homeostasis. The direct relationship between plasma renin activity and coronary blood flow suggests that the renin-angiotensin system may play an important role in coronary vasomotor regulation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Muscle glycogenolysis during exercise: dual control by epinephrine and contractions.

The interaction of epinephrine and contractions on muscle metabolism was studied in the isolated perfused rat hindquarter. Subtetanic contractions (180/min) through 20 min elicited glycogenolysis and increased phosphorylase a activity. In the soleus, a slow-twitch red muscle, these effects were transient, but when epinephrine at a physiological concentration (2.4 X 10(-8) M) was added to the perfusate, glycogenolysis and phosphorylase activity were sustained throughout contractions. At this high frequency of contractions, the effect of epinephrine was much smaller in the fast-twitch red fibers and not significant in the fast-twitch white fibers of the gastrocnemius muscle. However, during less frequent contractions (30/min) epinephrine increased glycogenolysis and phosphorylase a activity in fast-twitch muscle. The data suggest that epinephrine and muscle contractions exert a dual control of muscle glycogenolysis during exercise: contractions principally stimulate glycogenolysis early in exercise, and a direct effect of epinephrine on muscle is needed for continued glycogenolysis. In addition, epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated hindquarters and, under some conditions, it had a positive inotropic effect on contracting muscle.

Adenosine Triphosphate↗
PubMed1982

Systemic and regional hemodynamic effects of endogenous vasopressin stimulation in rats.

We investigated the systemic and regional hemodynamic alterations induced in normotensive anephric rats by stimulation of endogenous vasopressin with an acute sodium and fluid load and following vasopressin inhibition with a specific antagonist of its vasoconstricting action. Blood pressure and total peripheral resistance were significantly higher and cardiac output was lower in rats with stimulated vasopressin, and all were reversed to near control levels in rats receiving the vasopressin inhibitor. Regional blood flows were diminished in most organs and local vascular resistance was elevated compared with control animals, but the magnitude of change varied widely. In fact, heart blood flow did not decrease significantly and brain blood flow actually increased indicating small or no change in vascular resistance of these organs. Moreover, fractional distribution of the diminished cardiac output to these organs was significantly higher, so that blood flow to vital organs was maintained at the expense of blood flow to other tissues. In rats that received the vasopressin antagonist after the saline infusion, regional blood flows were similar to those of control animals. Blood pressures at the base line and after hypertonic NaCl infusion correlated closely with the corresponding plasma levels of control and stimulated vasopressin.

Animals↗
PubMed1982

Renin-angiotensin system inhibition in acute myocardial infarction in dogs. Effects on systemic hemodynamics, myocardial blood flow, segmental myocardial function and infarct size.

Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 micrograms/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p less than 0.05) decreased peripheral vascular resistance (from 3804 +/- 1158 to 2876 +/- 816 dy-sec-cm-5) (+/- SD) and mean aortic pressure (from 117 +/- 12 to 107 +/- 15 mm Hg), and increased cardiac output (from 2.63 +/- 0.67 to 3.12 +/- 0.74 l/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.

Animals↗
PubMed1982

Insulin infusion in conscious dogs. Effects on systemic and coronary hemodynamics, regional blood flows, and plasma catecholamines.

Cardiovascular actions of insulin were studied by intravenous infusions of insulin (4 and 8 mU/kg per min) in normal conscious dogs. This resulted in increases in cardiac output, heart rate, and left ventricular derivative of pressure with respect to time (dP/dt) and dP/dt/P, as blood glucose was reduced. The inotropic and chronotropic effects of insulin were not related to hypoglycemia, as they persisted even when blood glucose was restored to control values or when it was prevented from falling by a simultaneous infusion of glucose. These cardiac effects were accompanied by increases in plasma catecholamines, and were abolished by propranolol pretreatment. Both plasma epinephrine and norepinephrine increased during insulin hypoglycemia, but only norepinephrine increased during insulin infusion when euglycemia was maintained. Mean arterial blood pressure did not change significantly during insulin hypoglycemia, but rose if euglycemia was maintained, probably due to the selective increase in norepinephrine in the latter condition. A pressor response also occurred in propranolol-pretreated dogs during insulin hypoglycemia, but was abolished when the animals also had been pretreated with phentolamine, indicating that the vasoconstrictor action of insulin was mediated via alpha adrenergic receptors. Insulin infusion increased left ventricular work and myocardial blood flow in dogs with and without hypoglycemia. Myocardial blood flow, however, did not change significantly during insulin infusion in dogs pretreated with propranolol. As propranolol also diminished the inotropic response, it appears that the increase in myocardial blood flow caused by insulin in the normal dog is causally related to the increased myocardial metabolic demand. Insulin also produced vasomotor effects on other vascular beds. In skeletal muscle, blood flow was increased under all study conditions, except during insulin hypoglycemia after propranolol-pretreatment when unopposed alpha-mediated vasoconstriction was present. The persistent increase in flow during both alpha and beta adrenergic blockade suggests that insulin has a direct dilator effect on skeletal muscle vasculature. In the adrenal gland, flow was increased except during euglycemia, when no rise in plasma epinephrine was observed, suggesting coupling between adrenal flow and catecholamine release. In the splanchnic bed, flow was decreased during euglycemia, when plasma norepinephrine rose, and during beta adrenergic blockade with propranolol, when unopposed alpha-mediated vasoconstriction also predominated. A similar pattern was found in the kidney, except that renal blood flow also fell after combined alpha and beta adrenergic blockade. The results show that the vasomotor effects on regional flows are mediated both via adrenergic mechanisms, and in the case of skeletal muscle and kidney, via mechanisms unrelated to sympathetic stimulation.

Adrenergic beta-Antagonists↗
PubMed1982

Escape from mineralocorticoid excess: the role of angiotensin II.

Escape from the sodium-retaining action of mineralocorticoids coincides with the suppression of plasma renin and angiotensin II levels. The purpose of this study was to evaluate whether blockade of the renin system accelerates this escape. Eight male normotensive volunteers, aged 24--33 yr, were maintained during two subsequent periods of 12 days each, separated by 3--4 weeks, on a constant intake of sodium and potassium of 140 mmol/day. During both periods, fludrocortisone acetate (0.2 mg) was administered orally three times a day on days 4--12. In addition, on days 3--12, either a converting enzyme inhibitor (MK 421;20 mg orally, twice daily) or a placebo was added in double blind fashion and randomized sequence. During both periods, blood pressures were similar; they tended to increase slightly toward day 12. The weight increase did not differ between the two periods. With MK 421, angiotension II levels were significantly lower than with placebo on days 3--6 (P less than 0.001). On the same days, PRA was increased due to converting enzyme blockade. Despite the significantly different angiotensin II levels on days 3--6, daily urinary sodium excretion on all individual days as well as cumulative sodium balance were the same during both periods. Therefore, we could find no evidence in man that suppression of circulating angiotensin II levels is causally related to escape from mineralocorticoid excess.

Adult↗
PubMed1982

Hypertension and age: clinical and biochemical correlates.

Plasma renin activity, aldosterone and norepinephrine levels were determined in 247 ambulatory hypertensive patients divided into young, middle aged, and old groups. PRA and the increase of PRA after furosemide were higher in the younger; NE was higher in the old group. Some relationships may be inherent in aging and not necessarily confined to hypertensives. This may explain discrepancies between reports by investigators who studied homogenous groups classified in different ways.

Adult↗
PubMed1982

Effects of the new oral angiotensin converting enzyme inhibitor MK-421 in human hypertension.

"MK-421" a new oral converting enzyme inhibitor was administered to 16 hypertensive patients in doses ranging between 2.5-40 mg once daily for periods of 6-18 weeks. The blood pressure, plasma renin activity, plasma angiotensin II, aldosterone and angiotensin converting enzyme activity were assessed before and during treatment. Blood pressure normalized in 11 patients and decreased significantly in the remaining 5, without significant changes in heart rate or orthostatic hypotension. At 24 hrs after the first effective dose, plasma renin activity remained elevated to 228% whereas plasma angiotensin II was suppressed to 58%, aldosterone was suppressed to 40% and angiotensin converting enzyme activity was suppressed to 16% of the baseline. Magnitude of blood pressure decrement achieved with the maximal dose did not correlate with baseline plasma renin activity levels. No side-effects were noted during the 6-18 week period of observation.

Administration, Oral↗
PubMed1982

Possible mechanisms of sodium-dependent hypertension: volume expansion or vasoconstriction?

A series of experiments was designed to explore the mechanisms contributing to hypertension caused by an acute or chronic sodium load. Acute salt-loading in totally or subtotally nephrectomized animals caused hypertension mediated partly through stimulation of excessive vasopressin release and partly through adrenergic stimulation. Chronic high-salt diet in rats submitted to partial nephrectomy, mineralocorticoid excess or one-kidney-one-clip renovascular hypertension caused blood pressure elevation mediated through a central neurogenic mechanism that could be reversed by administration of an inhibitor of phenylethanolamine-N-methyltransferase, the enzyme catalyzing conversion of norepinephrine to epinephrine. Thus, two vasopressor mechanisms were stimulated by sodium excess: an acute, transient, partly vasopressin-mediated phase seemed to be followed by a chronic phase mediated through stimulation of central sympathetic neurons. In neither phase was blood pressure related to intravascular fluid volume expansion.

Animal Feed↗
PubMed1982

Evidence for a sodium-induced activation of central neurogenic mechanisms in one-kidney, one-clip renal hypertensive rats.

The mechanisms sustaining high blood pressure in conscious one-kidney, one-clip Goldblatt rats were evaluated with the use of SK&F 64139, a phenylethanolamine N-methyltransferase inhibitor capable of crossing the blood-brain barrier and of captopril, an angiotensin converting enzyme inhibitor. The rats were studied 3 weeks after left renal artery clipping and contralateral nephrectomy. During the developmental phase of hypertension, two groups of rats were maintained on a regular salt (RNa) intake, whereas two other groups were given a low salt (LNa) diet. On the day of the experiment, the base-line mean blood pressure measured in the LNa rats (177.4 +/- 5.2 mm Hg, mean +/- S.E., n = 15) was similar to that measured in the RNa rats (178.7 +/- 5.4 mm Hg, n = 16). SK&F 64139 (12.5 mg p.o.) induced a significantly more pronounced (P less than .001) blood pressure decrease in the RNa rats (-25.6 +/- 3.6 mm Hg, n = 8) than in the LNa rats (-4.3 +/- 3.3 mm Hg, n = 7) during a 90-min observation period. On the other hand, captopril (10 mg p.o.) normalized blood pressure in LNa rats (n = 8), but produced only a 13.4 mm Hg blood pressure drop in RNa rats (n = 8). RNa rats treated with SK&F 64139 were found to have decreased phenylethanolamine N-methyltransferase activity by an average 80% in selected brain stem nuclei when compared with nontreated rats. No significant difference in plasma catecholamine levels was found between the RNa and LNa rats. These results suggest that, in this experimental model of hypertension, the sodium ion might increase the model of hypertension, the sodium ion might increase the vasoconstrictor contribution of the sympathetic system via a centrally mediated neurogenic mechanism while at the same time it decreases the renin-dependency of the high blood pressure.

Animals↗
PubMed1982

Hypertension in a patient with hypercalcemia: captopril and verapamil.

A 38-year-old woman with hypercalcemia, severe hypertension, and high renin levels was treated with the angiotensin-converting enzyme inhibitor captopril. This therapy, together with spironolactone, normalized blood pressure (BP), but even with three daily administrations of the converting enzyme inhibitor, intermittent rebound hypertension could not be avoided. The administration of only verapamil, an antagonist of calcium transport, did not induce BP control, but when verapamil therapy was combined with administration of captopril and spironolactone, BP could be normalized with only twice-daily administration of the converting enzyme inhibitor. Thus, high plasma calcium levels seem to sensitize the arterioles to the intermittent increase of angiotensin II levels that accompanies captopril therapy.

Adult↗