Effects of captopril and enalapril on regional vascular resistance and reactivity in spontaneously hypertensive rats.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004656:Enalapril; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008863:Microspheres; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011674:Pulse / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D012083:Renin / Q000097:blood; D013152:Splanchnic Circulation; D013722:Teprotide; D014463:Ultrasonography; D014655:Vascular Resistance / Q000187:drug effects*
D004151:Dipeptides; D009842:Oligopeptides; D004656:Enalapril; D011392:Proline; D002216:Captopril; D013722:Teprotide; D012083:Renin; D009638:Norepinephrine