Chronic captopril administration decreases vasodilator responses in skeletal muscle arterioles.

Changes in arteriolar reactivity to dilator agonists were assessed in the cremaster muscle of Sprague-Dawley rats fed normal rat chow with captopril (100 mg/kg/day) in the drinking water for 8 weeks and in nontreated controls. The in situ cremaster muscle was prepared, superfused with physiologic salt solution, and arteriolar diameter was measured using television microscopy. Changes in the diameter of distal arterioles in response to topical application of iloprost, forskolin, cholera toxin, acetylcholine, and nitroprusside were measured with a video micrometer. Arteriolar responses to each of the vasodilator agonists used in this study were significantly reduced in the captopril-treated rats, relative to the untreated controls. The maximum dilation of the arterioles, determined during superfusion with Ca2+-free physiologic salt solution containing 10(-4) mol/L adenosine, was also reduced in the captopril-treated rats, suggesting structural remodeling of the arteriolar wall. These observations indicate that chronic angiotensin converting enzyme inhibition with captopril leads to significant alterations in arteriolar structure and reactivity, and that angiotensin II may play a protective role in maintaining normal vascular structure and vasodilator reactivity in the microcirculation.