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The effects of short-term oral treatment with captopril and enalapril (two angiotensin-I-converting-enzyme inhibitors [ACEIs] that were administered in equipotent antihypertensive doses) on the systemic vasopressor response and on the renal, mesenteric, and hindlimb vascular responses to cirazoline and UK-14,304 (alpha 1- and alpha 2-adrenergic receptor-specific agonists, respectively) were investigated in adult pithed spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain. In the nonbinephrectomized animal, captopril and enalapril reduced to the same extent the systemic blood pressure and renal and hindlimb vascular resistances. They also decreased to the same extent systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304, especially in the renal and mesenteric vascular beds. Simultaneously, the effects of angiotensin I and angiotensin II on the pressor response were abolished and almost not modified. In the binephrectomized animals, captopril and enalapril no longer reduced the systemic blood pressure and regional vascular resistances, but whereas the sympathoinhibitory effect of captopril vs the systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304 persisted, those of enalapril disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

MK 421, 25 mg/kg, administered daily by gavage to young spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited genetic hypertension development. Since heart rate and cardiac index were not drug affected, prevention of genetic hypertension development was solely related to an early, potent and long-lasting limitation of the progressive increase in peripheral resistance which normally develops in SHRs during ageing. MK 421 slightly enhanced vascular responsiveness to exogenous norepinephrine and angiotensin II and reduced myocardial hypertrophy. Plasma renin concentration was increased. MK 421 slightly reduced body growth but did not affect fluid intake, urinary volume and urinary ADH, demonstrating that no water or salt retention developed. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after treatment discontinuation.

The effects of a short-term oral treatment with captopril or enalapril, two converting enzyme inhibitors (CEIs) administered in equipotent antihypertensive doses, on the systemic vasopressor and on the renal, mesenteric and hind-limb vascular responses to cirazoline and UK 14304, respectively alpha1- and alpha2- adrenoceptor specific agonists, were investigated in the adult pithed SHR. Cirazoline and UK 14304 induced vasoconstrictor responses in the three investigated territories, demonstrating the location and a functional role at these levels of the two sub-types of alpha-adrenoceptors. Both captopril and enalapril reduced, to the same extent, the systemic pressor and the regional vasoconstrictor responses, especially in the renal and mesenteric territories, elicited by cirazoline and UK 14304, demonstrating that both subtypes of alpha-adrenoceptors are involved in the CEIs-induced attentuation of sympathetic responses.

The present study compares the effects of short-term treatments with captopril and enalapril, administered in equipotent antihypertensive doses, on the regional vascular resistances and on the regional vascular responsiveness to vasopressor agents of adult spontaneously hypertensive rats (SHRs). Three groups of animals were treated by gavage with captopril (100 mg/kg), enalapril (25 mg/kg), or distilled water for 8 days. Arterial blood pressure (BP), heart rate (HR), plasma renin concentration (PRC), and plasma converting-enzyme activity (CEA) were measured. Cardiac index (CI), total peripheral resistance (PR), and organ flow distribution were determined using microspheres. Renal and mesenteric vascular responsiveness to vasopressor agents was evaluated by continuous measurement of renal and mesenteric blood flows with miniaturized pulsed Doppler flow probes. Data showed that in the anesthetized SHR the two drugs induced similar reductions in BP, PR, and HR, without affecting CI. They simultaneously produced a strong converting-enzyme inhibition as evidenced by the suppression of angiotensin I effects accompanied by a potentiation of angiotensin II responses, a reduction in CEA, and an increase in PRC. Organ flows were similarly and homogeneously increased, especially in the kidneys, in both treated groups. Norepinephrine (NE) vasoconstrictor responses were abolished in the mesenteric vascular bed by both drugs, but in the renal, NE responses although completely abolished by captopril were only partially reduced by enalapril. It thus appears that diminished vascular responsiveness to NE, especially in the case of captopril, is probably involved along with converting-enzyme inhibition in the antihypertensive action of converting enzyme inhibitors (CEI), the mechanism of the difference between captopril and enalapril remaining still speculative.

MK 421, at the dose of 25 mg/kg, administered daily by gavage to spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited development of genetic hypertension. Since heart rate and cardiac and systolic indexes were not affected by the drug, prevention of genetic hypertension development was solely related to an early, potent and long-lasting reduction of the progressive increase of the peripheral resistance which generally develops in SHRs during ageing. MK 421 reduced body growth but did not modify fluid intake, plasma NA+ and urine volume, thus water and salt retention did not develop. MK 421 enhanced vascular responsiveness to norepinephrine and angiotension II and reduced myocardial hypertrophy. Plasma renin concentration was increased and urinary antidiuretic hormone did not change. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after discontinuation of treatment.