Chronic captopril administration decreases vasodilator responses in skeletal muscle arterioles

Changes in arteriolar reactivity to dilator agonists were assessed in the c remaster 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 sa lt solution, and arteriolar diameter was measured using television microsco py. Changes in the diameter of distal arterioles in response to topical app lication of iloprost, forskolin, cholera toxin, acetylcholine, and nitropru sside were measured with a video micrometer. Arteriolar responses to each o f the vasodilator agonists used in this study were significantly reduced in the captopril-treated rats, relative to the untreated controls. The maximu m dilation of the arterioles, determined during superfusion with Ca2+-free physiologic salt solution containing 10(-4) mol/L adenosine, was also reduc ed in the captopril-treated rats, suggesting structural remodeling of the a rteriolar wall. These observations indicate that chronic angiotensin conver ting enzyme inhibition with captopril leads to significant alterations in a rteriolar structure and reactivity, and that angiotensin II may play a prot ective role in maintaining normal vascular structure and vasodilator reacti vity in the microcirculation. (C) 1999 American Journal of Hypertension, Lt d.