When administered to young spontaneously hypertensive rats (SHRs), dihydralazine (25 mg kg-1, daily) and captopril (100 mg kg-1, daily) prevent with the same efficacy genetic hypertension development (GHD). Dihydralazine treatment increased vascular mesenteric compliance, as shown by a significant decrease in the stiffness of the vessels (-27%), and induced slight reductions in contractility (-12%) and in wall to lumen (W/L) ratio (-15%). After treatment withdrawal, all these parameters returned to control values within 7 weeks, as did blood pressure. Captopril treatment also strongly increased the mesenteric vessels compliance, vessel stiffness being decreased by 16%, and reduced their contractility (-15%) and their W/L ratio (-30%). These effects as well as those exerted on blood pressure persisted up to 7 weeks after treatment ceased although there was a slight trend to a progressive reduction in the intensity of both phenomena. These experiments show that captopril but not dihydralazine has a long-lasting effect in opposing the functional and morphological vascular alterations occurring during GHD in SHRs and this phenomenon probably contributes to a large extent to the sustained preventive effects of the drug against GHD.

/pdf/compared-myocardial-and-vascular-effects-of-captopril-and-4kwarpubxc.pdf

Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats

Angiotensin converting enzyme inhibitors represent a new class of agents which were designed to retain only that unique property. Because of this inhibition, administration of these agents results in the significant reduction of elevated blood pressure of various etiologies and in the amelioration of symptoms associated with congestive heart failure resistant to digitalis glycosides and diuretics. The mechanism(s) of action is not entirely certain but almost certainly resides in the inhibition of ACE. Certainly, the future will see still further advances made in this therapeutic area as well as with other inhibitors of the renin-angiotensin system.

Angiotensin converting enzyme (ACE) inhibitors

We examined the effects of physiologic infusions of arginine vasopressin (AVP) on cardiovascular hemodynamics and on reflex responses initiated by decreasing cardiopulmonary baroreceptor stimulation (with lower body negative pressure) in 10 healthy, captopril-pretreated young men (19-27 yr). Their responses were compared with those of four volunteers given isosmotic infusion. Heart rate, stroke volume, blood pressure, and forearm blood flow were measured by electrocardiography, impedance cardiography, radial artery cannulation, and strain gauge plethysmography. Two 55-min infusions of AVP at rates of 0.15 and 0.40 ng/kg per min increased average plasma concentrations from control levels of 5 pg/ml to 18 and 36 pg/ml, respectively. These infusions resulted in progressive reductions of heart rate and cardiac output and increases of forearm and total peripheral resistance. Blood pressure increases were significant only during the larger AVP infusion rate. Lower body negative pressure provoked reflex increases of total peripheral resistance. These increases were enhanced 60% during AVP infusion compared with increases during control (pre-AVP). Baseline measurements and reflex responses were unchanged by isosmotic infusions. These results demonstrate that AVP has profound effects on cardiovascular function and augments cardiopulmonary baroreflex-mediated increases of peripheral resistance in man.

/pdf/vasopressin-reduces-cardiac-function-and-augments-2f7mxxtw1j.pdf

Vasopressin reduces cardiac function and augments cardiopulmonary baroreflex resistance increases in man.

Corcoran Lecture. Angiotensin-converting enzyme inhibition and the heart.

• Blood pressure and heart rate exhibit a circadian rhythm, with both rising rapidly during the morning hours and then decreasing throughout the day to a nadir around 3 AM. Current evidence suggests a possible link between cardiovascular events, such as myocardial infarction and sudden cardiac death, which have been shown to occur most frequently during the morning hours, and the rapid rise in blood pressure and heart rate during this same time period. We review data from ambulatory blood pressure studies to ascertain which antihypertensive agents provide the most satisfactory control of blood pressure and heart rate during the hours of 6 AM to 12 noon. Of the forms of drug therapy studied, labetalol, a combined α- and β-blocker, and two calcium channel blockers, nifedipine and verapamil, appear to be the most effective in blunting the rise in arterial blood pressure during these critical morning hours. ( Arch Intern Med 1988;148:2547-2552)

Effects of antihypertensive agents on circadian blood pressure and heart rate patterns. Review.

To study the influence of acute and chronic angiotensin-converting enzyme blockade on the pressor response to exogenous angiotensin II, vasopressin and norepinephrine, we gave normal female Wistar rats 100 mg of captopril or 1 ml of 5% glucose twice daily by gavage for 2 weeks. On the 15th day, rats were anesthetized with pentobarbital, and dose-response curves to angiotensin II, lysine-vasopressin, and norepinephrine were obtained before and after intraperitoneal injection of 100 mg/kg of captopril or 1 ml of 5% glucose. Acute as well as chronic converting enzyme blockade enhanced the pressor response to exogenous angiotensin II. Similarly, sensitivity to exogenous vasopressin was increased by both acute and chronic converting enzyme inhibition. In contrast, chronic converting enzyme blockade significantly blunted the response to exogenous norepinephrine, whereas acute blockade tended to accentuate its pressor effect. These results suggest that chronic angiotensin-converting enzyme blockade may partly inhibit sympathetic activity which, in turn, might contribute to the antihypertensive efficacy of this therapeutic approach. These results also point to an important physiological interaction between the two pressor hormones, angiotensin II and vasopressin.

The opposing effects of chronic angiotensin-converting enzyme blockade by captopril on the responses to exogenous angiotensin II and vasopressin vs. norepinephrine in rats.

F Spertini

Papers

The opposing effects of chronic angiotensin-converting enzyme blockade by captopril on the responses to exogenous angiotensin II and vasopressin vs. norepinephrine in rats.