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Biomedical subjects

H Gavras

Publications and source records attributed to H Gavras.

At least 253 records · Page 14Linked to original sources
PubMed1978

Long-term treatment of hypertension in man by an orally active angiotensin-converting enzyme inhibitor.

1. Captopril or SQ 14 225, administered orally twice a day, reduced the blood pressure of hypertensive patients whatever their clinical diagnosis and even when their plasma renin activity was 'normal' or low. 2. Long-term administration of captopril, either alone or together with diuretics, provides a powerful new tool with which to treat ambulatory hypertensive patients. 3. The renin system may play an important role in maintaining blood pressure in a majority of hypertensive patients.

Adult↗
PubMed1978

Congestive heart failure in normotensive man. Haemodynamics, renin, and angiotensin II blockade.

The role of the renin angiotensin system was evaluated in 18 normotensive patients with chronic congestive heart failure and in 5 controls. No correlation was observed between plasma renin activity and cardiac index. There was a significant inverse correlation between renin and pulmonary capillary wedge pressure (r = -0.61, P less than 0.01). Renin values of the patients appeared to be increased when compared with controls with similar left ventricular filling pressure. Specific angiotensin II inhibition by saralasin decreased arterial pressure in 8 out of 14 patients: their renin was significantly higher than that of the remaining 6 patients (P less than 0.01). The 2 patients with the lowest renin levels responded to saralasin with a blood pressure increase. Left ventricular filling pressure decreased in all but these latter 2 patients with either little change or an increase in stroke volume. Thus, renin levels appear to be increased in normotensive patients with congestive heart failure when related to left ventricular filling pressure. Renin via angiotensin II plays a role in the blood pressure control of many patients with congestive heart failure. In some patients angiotensin II blockade appears to improve cardiac function by unloading the left ventricle.

Adult↗
PubMed1978

Angiotensin converting enzyme inhibition in patients with congestive heart failure.

The etiology of afterload elevation in congestive cardiac failure is unclear, but experimental evidence suggests a role for the renin-angiotensin system in maintaining elevated peripheral vascular resistance. The angiotensin converting enzyme inhibitor SQ20,881 was administered to eight patients with congestive cardiac failure (four hypertensives, four normotensives) during or one day after diagnostic cardiac catheterization. Various hemodynamic measurements performed before and during blockade indicate that this agent caused improvement in cardiac function in all patients by decreasing afterload. This improvement correlated with the decrease in total vascular resistance but was independent of the baseline blood pressure and plasma renin activity. These results suggest that inhibition of angiotensin converting enzyme is a worthwhile approach to the treatment of congestive heart failure, although its exact mechanism of action remains unclear.

Aged↗
PubMed1978

Renin-angiotensin system inhibition in conscious sodium-depleted dogs. Effects on systemic and coronary hemodynamics.

The role of the renin-angiotensin system in the regulation of the systemic and coronary circulations during sodium depletion was studied in conscious normotensive dogs by i.v. administration of teprotide (0.5 mg/kg), an angiotensin-converting enzyme inhibitor, and saralasin (0.05-5 mug/kg per min), an angiotensin-receptor antagonist. Sodium depletion was produced by administering a low sodium diet and furosemide for 5 days. Administration of both teprotide and saralasin lowered systemic arterial blood pressure and total peripheral vascular resistance. Simultaneously, cardiac output increased, but left ventricular end-diastolic pressure, dP/dt, and dP/dt/P did not change significantly. Furthermore, both agents reduced diastolic coronary vascular resistance and increased coronary blood flow, but did not affect myocardial oxygen consumption, left ventricular work, or myocardial efficiency. These systemic and coronary vasodilator effects of teprotide and saralasin, however, were not observed in normal dogs on a regular sodium diet; in this group, the only effect noted was a slight increase in arterial pressure during saralasin infusion. Arterial plasma concentration of norepinephrine did not differ between normal and sodiumdepleted dogs, nor did it change significantly after teprotide administration. These results suggest that, during salt depletion, angiotensin II exerts an active vasoconstrictor action on the systemic and coronary vessels, but has no significant effects on myocardial contractility or energetics. It also appears likely that the increase in cardiac output observed in sodiumdepleted dogs after angiotensin inhibition was caused, at least in part, by the decrease in systemic arterial pressure.

Angiotensins↗
PubMed1978

Renin-angiotensin system inhibition in conscious dogs during acute hypoxemia. Effects on systemic hemodynamics, regional blood flows, and tissue metabolism.

The role of the renin-angiotensin system in mediating the circulatory and metabolic responses to hypoxia was studied in three groups of conscious dogs that were infused continuously with normal saline, teprotide (10 mug/kg per min), and saralasin (1 mug/kg per min), respectively. Hypoxia was produced by switching from breathing room air to 5 or 8% oxygen-nitrogen mixture. Plasma renin activity increased from 2.3+/-0.4 to 4.9+/-0.8 ng/ml per h during 8% oxygen breathing, and from 2.8+/-0.4 to 8.4+/-1.8 ng/ml per h during 5% oxygen breathing. As expected, cardiac output, heart rate, mean aortic blood pressure, and left ventricular dP/dt and dP/dt/P increased during both 5 and 8% oxygen breathing in the saline-treated dogs; greater increases occurred during the more severe hypoxia. Teprotide and saralasin infusion diminished the hemodynamic responses to 5% oxygen breathing, but did not affect the responses to 8% oxygen breathing significantly. In addition, the increased blood flows to the myocardium, kidneys, adrenals, brain, intercostal muscle, and diaphragm that usually occur during 5% oxygen breathing were reduced by both agents. These agents also reduced the increases in plasma norepinephrine concentration during 5% oxygen breathing, but had no effects on tissue aerobic or anaerobic metabolism. In dogs pretreated with propranolol and phentolamine, administration of teprotide (0.5 mg/kg) during 5% oxygen breathing reduced mean aortic blood pressure and total peripheral vascular resistance, and increased cardiac output and heart rate, but did not affect left ventricular dP/dt, dP/dt/P, and end-diastolic pressure. Simultaneously, renal and myocardial blood flows increased and myocardial oxygen extraction decreased, while myocardial oxygen consumption did not change significantly. These results suggest that the renin-angiotensin system plays an important role in the hemodynamic responses to severe hypoxia. It appears that angiotensin not only exerts a direct vasoconstrictor action, especially upon the coronary and renal circulations, but also potentiates the cardiovascular effects of sympathetic stimulation that occur during severe hypoxia.

Angiotensins↗
PubMed1978

Angiotensin II blockade in congestive heart failure.

Five of 11 normotensive patients with congestive heart failure responded to an infusion of the specific angiotensin II antagonist, saralasin, by reducing systemic vascular resistance from 2274 +/- 418 to 1690 +/- 351 dynes/sec/cm-5 (mean +/- standard error). This decrease was accompanied by a reduction in left ventricular filling pressure from 19.4 +/- 5.9 to 11.6 +/- 4.0 mm Hg, an increase in cardiac index from 2.2 +/- 0.4 to 2.7 +/- 0.4 l/min/m2 and a decrease in mean arterial pressure from 95 +/- 9.8 to 86 /+- 8.6 mm Hg. In the other 6 patients with congestive heart failure and in 4 controls, saralasin produced either no change or slight increases in systemic vascular resistance. Plasma renin activity did not differentiate responders from non-respnders. Specific inhibition of angiotensin may provide a means for reducing inappropriately high peripheral resistance in some patients with congestive heart failure.

Adult↗
PubMed1978

Relationship of basal plasma norepinephrine to blood pressure, plasma renin activity, mineralocorticoids, and plasma volume in essential hypertension.

The basal levels of plasma norepinephrine have been measured in 113 carefully characterized patients with essential hypertension, and the results have been correlated with the PRA sub-grouping and the levels of blood pressure, plasma aldosterone, plasma 18-hydroxy-deoxycorticosterone, and plasma volume. In addition, the influence of furosemide on plasma norepinephrine concentration has been assessed. Essential hypertensives, when considered as a whole, did not exhibit any significant abnormality in basal plasma norepinephrine concentration, but interesting alterations were observed in certain specific sub-groups. High renin patients had significantly elevated levels of basal plasma norepinephrine. In addition, a sub-group of the low renin population who were relatively young had reduced plasma norepinephrine conentration. In these individuals with both reduced PRA and plasma norepinephrine, the levels of both increased concomitantly to the normal range with marked salt depletion. Furosemide administration induced increases in plasma norepinephrine in all PRA sub-groups. Plasma norepinephrine correlated significantly with blood pressure in normal and low renin hypertensives, but the relationships were confined only to male subjects. Significant correlations were also observed between plasma norepinephrine and plasma aldosterine in males with normal PRA but not in the other sub-categories. No significant relationships between plasma volume and either plasma norepinephrine or blood pressure could be detected. Plasma 18-hydroxy-deoxycorticosterone was greater in males as compared with females and appeared elevated above control levels in normal and high renin essential hypertensives. Significant positive correlations between plasma aldosterone and plasma 18-hydroxy-deoxycorticosterone were observed in both males and females with normal renin hypertension. These studies have demonstrated abnormalities in basal plasma norepinephrine concentration in certain patients with essential hypertension. They also suggest that the levels of blood pressure and plasma aldosterone may be related to peripheral sympathetic activity in essential hypertension.

18-Hydroxydesoxycorticosterone↗
PubMed1977

Angiotensin II inhibition. Treatment of congestive cardiac failure in a high-renin hypertension.

A patient with intractable congestive cardiac failure secondary to renovascular hypertension and severe coronary artery disease was infused with the competitive antagonist of angiotensin II, saralasin acetate. The infusion produced an impressive increase in cardiac output and left ventricular stroke work index in parallel with a striking decrease in the systemic and pulmonary vascular resistance, the coronary resistance, and the myocardial oxygen consumption. It is suggested that angiotensin inhibition may present advantages over other forms of treatment of congestive cardiac failure in selected cases.

Angiotensin II↗
PubMed1977

A specific orally active inhibitor of angiotensin-converting enzyme in man.

An orally active inhibitor of the angiotensin-converting enzyme, SQ 14,225 (D-2-methyl-3-mercaptopropanoly-L-proline), was administered to fourteen normal male volunteers to evaluate its safety and efficacy in inhibiting pressor responses to exogenous angiotensin I. SQ 14,225 produced significant blockade within 15 min of oral administration. The magnitude and duration of inhibition were dose-related. After a dose of 20 mg, complete blockade was observed for more than 2 h and partial inhibition for over 4 h. There was no effect on pressor responses to angiotensin II. SQ 14,225 promises to provide a new approach to the diagnosis and treatment of disorders involving over-activity of the renin-angiotensin system.

Administration, Oral↗
PubMed1977

Angiotensin II blockade in normal man: interaction of renin and sodium in maintaining blood pressure.

Nine normotensive volunteers underwent six days of sodium-depletion followed by six days of sodium-repletion. On days six and twelve, the angiotensin II inhibitor, sar1-ala8-angiotensin II (saralasin), was infused i.v. and the blood pressure monitored with the subjects first in supine and then in upright position. The degree of induced sodium-depletion was varied over a considerable range in order to determine the level of sodium balance which is critical for maintaining blood pressure in the absence of the pressor action of angiotensin II. Five subjects had a cumulative sodium loss of more than 200 mEq, mainly because of more vigorous diuretic treatment; upon infusion of saralasin, four exhibited marked hypotension in the erect position. The fifth became deeply hypotensive while still supine and was unable to stand up. Hypotension occurred in spite of clinical evidence of catecholamine oversecretion. In the four patients who had urinary sodium losses of less than 200 mEq, infusion of the inhibitor did not reduce their blood pressure. Following sodium-repletion, none of the nine subjects exhibited a blood pressure response to the inhibitor. These results suggest that angiotensin II plays an active role in sustaining normal blood pressure only under conditions of considerable sodium-depletion.

Adult↗
PubMed1977

Is elevated plasma renin activity of prognostic importance in progressive systemic sclerosis?

The pathologic lesions of the kidney in scleroderma in many respects resemble those of malignant hypertension, perhaps even in the absence of comparable blood pressure elevation. Because the malignant vascular changes have been related to hyperreninemia, we measured plasma renin activity in 23 patients with scleroderma with or without hypertension and/or renal failure. We found that high renin levels in most cases shortly preceded or coincided with a phase of sudden deterioration of the disease, characterized by a rapidly progressive renal failure. The outcome of this phase was invariably fatal, except for two patients in whom bilateral nephrectomy successfully arrested the rapid downhill course. These findings suggest that an unexplained increase in circulating renin levels in an otherwise stable patient with scleroderma may be taken as a possible marker of imminent deterioration requiring close monitoring and immediate therapeutic intervention.

Adult↗
PubMed1976

[Angiotensin II inhibitors for the diagnosis and treatment of hypertension].

Specific antagonists of the renin angiotensin system have been used to investigate the role of this hormonal system in blood pressure homeostasis and in different types of experimental and clinical hypertension. Using this approach it was possible to show that renin via angiotensin participates actively in blood pressure maintenace, particularly following sodium depletion. Such antagonists, if available for oral administration and taken together with a diuretic, would be useful therapeutically.

Adult↗
PubMed1976

Reciprocal relation between renin dependency and sodium dependency in essential hypertension.

To investigate the roles of angiotensin II and sodium in essential high-renin, normal-renin and low-renin hypertension, 14 patients received the competitive antagonist of angiotensin II, saralasin, during periods of sodium depletion and repletion. Blood-pressure response to saralasin was determined by the state of sodium balance. Patients from all three renin subgroups exhibited a fall in blood pressure when sufficiently sodium depleted, and an elevation in blood pressure when sodium replete or insufficiently depleted. However, those with low renin required loss of substantially more sodium (sufficient to elicit compensatory stimulation of renin) before depletion could be achieved. In patients with essential hypertension of all three renin subgroups, sodium balance determines the degree of participation of the renin-angiotensin system in sustaining high blood pressure. Even the low-renin type can become renin dependent with sufficient sodium depletion.

Adult↗
PubMed1976

Determination of renin-dependency and sodium-dependency in the three renin sub-groups of essential hypertension.

1. In all three renin sub-groups of essential hypertension, the state of sodium balance determines the degree of participation of the renin-angiotensin system in sustaining high blood pressure. 2. Even the low-renin type can become renin-dependent when sufficient sodium depletion has bee achieved. 3. The main difference between patients of these sub-groups appears to be their variable capacity to become depleted of sodium under standard dietary regimens.

Aldosterone↗