Graded regional vasodilation with converting enzyme inhibitors in conscious spontaneously hypertensive rats

The present study was designed to examine the effects of two different converting enzyme inhibitors on regional hemodynamics in conscious spontaneously hypertensive rats. Rats were chronically instrumented with miniaturized pulsed Doppler flow probes for measurement of renal, mesenteric and hindquarters blood flow. Equidepressor doses of captopril (10 mg/kg) or a potent new converting enzyme inhibitor, Wy-44,221 [(-)-(S)-2,3-dihydro-1-[(S)-3-mercapto-2-methyl-1-oxypropyl]-1 H-indoline-2-carboxylic acid] (2 mg/kg) were administered by i.a. bolus injection. The converting enzyme inhibitors caused a reduction in mean arterial pressure, which was accompanied by a tachycardia. Renal blood flow was significantly increased by approximately 30 to 37% within 5 min after administration of the converting enzyme inhibitors, and renal vascular resistance was reduced. The renal hemodynamic effects were sustained for the 45-min duration of the experiment. Pretreatment with an angiotensin II receptor antagonist markedly attenuated the renal vasodilator effects of Wy-44,221, whereas antagonism of kinin or prostaglandin synthesis failed to diminish the renal effects of Wy-44,221. Both converting enzyme inhibitors also caused a significant but transient reduction in mesenteric vascular resistance, but had no significant effect on hindquarter hemodynamics. These data indicated that the converting enzyme inhibitors in conscious spontaneously hypertensive rats caused a prolonged increase in renal blood flow as a result of removing the renal vasoconstrictor effects of angiotensin II. These data further suggest that converting enzyme inhibitors exerted graded actions on regional vascular resistance with renal greater than mesenteric greater than hindquarters dilation.