Antihypertensive therapy with MK 421: angiotensin II--renin relationships to evaluate efficacy of converting enzyme blockade.

Nineteen hypertensive patients were treated with increasing doses of the new angiotensin-converting enzyme inhibitor MK 421. Twenty milligrams orally reduced blood pressure from 180/112 +/- 6.8/3.

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 .

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.

Pre- and postsynaptic effects of SKF64139, a phenylethanolamine N-methyltransferase inhibitor, in conscious normotensive rats.

We investigated in conscious normotensive rats the effect of SKF64139 (2 mg i.v.), a potent phenylethanolamine N-methyltransferase (PNMT) inhibitor, on blood pressure responses to norepinephrine (40, 80, and 160 ng i.

Reversal of experimental acute cerebral vasospasm by angiotensin converting enzyme inhibition.

We tested the hypothesis that cerebral arteriospasm developing after rupture of a subarachnoid aneurysm may be due to the vasoconstrictor effect of locally generated angiotensin II. Ten dogs had subarachnoid hemorrhage simulated by intracisternal introduction of 2 ml autologous blood, and were followed by cineangiography. Thirty minutes later, when acute arteriospasm was established, seven dogs received injection of the angiotensin converting enzyme inhibitor teprotide and 3 control dogs received normal saline.

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.

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.

Interaction of the sympathetic nervous system with vasopressin and renin in the maintenance of blood pressure.

To evaluate the partial contributions and interaction of three vasopressor systems in blood pressure maintenance, nephrectomized rats and rats with intact kidneys were submitted sequentially to catecholamine depletion, elimination of vasopressin's vasoconstrictor action, and (for those with kidneys in situ) angiotensin blockade. Catecholamine depletion decreased blood pressure and stimulated vasopressin levels in all rats, but significantly more so in the anephric ones. Subsequent injection of an antagonist to the vasopressor effect of vasopressin produced a lasting fall of blood pressure in anephric rats, but only transient fall in those with intact kidneys.

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.

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.

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.

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.

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.

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.

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.

RHC 3659: a new orally active angiotensin converting enzyme inhibitor in normal volunteers.

1 The new converting enzyme inhibitor RHC 3659 was tested in 15 male volunteers. The study consisted of two parts: first, the ability of a single oral dose (5, 10, 20, 40 or 80 mg) to inhibit the pressor response to exogenous angiotensin I was tested with blood pressure and heart rate monitored continuously through an intraarterial catheter. A dose-related shift to the right of the pressor response curve to angiotensin I was observed with a peak occurring within 0.

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

1. The effects of the new oral angiotensin-converting enzyme (ACE) inhibitor MK-421 on blood pressure, plasma renin activity, angiotensin-II, aldosterone and converting enzyme activity were assessed in 16 hypertensive patients followed for 6--18 weeks. 2.

Reversal of experimental delayed cerebral vasospasm by angiotensin-converting enzyme inhibition.

Delayed cerebral vasospasm is an important determinant of the clinical outcome after subarachnoid hemorrhage, but its prevention and treatment has met with limited success. Since cerebral arteries were found to be sensitive to the vasoconstrictor effect of angiotensin II, the possibility of angiotensin's contribution to this vasospasm was investigated. Delayed cerebral arterial spasm was documented angiographically 72 hours after introduction of blood in the subarachnoid space of dogs.

Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update.

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.

Antihypertensive effect of the new oral angiotensin converting enzyme inhibitor "MK-421".

The effects of the new oral converting enzyme inhibitor "MK-421" on blood pressure, plasma renin activity, plasma angiotensin II, aldosterone, and angiotensin converting enzyme were assessed in 16 hypertensive patients. Maximum (maintenance) doses ranged from 2.5 mg-40 mg daily.