The purpose of this study was to evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on collateral-dependent blood flow (BF) during exercise. Adult male Sprague-Dawley rats (approximately 320 g) were fed zabicipril, an ACE inhibitor, mixed with powdered food at 0.0, 0.3, and 3.0 mg.kg-1 x day-1 (n = 12/group) for 5-7 days. Under ketamine-acepromazine anesthesia, the carotid and caudal arteries were catheterized for BF determination, and both femoral arteries were ligated to remove the primary route for BF to the distal limb tissue. Later on the same day, collateral-dependent hindlimb BF was determined at two treadmill speeds (15 and 25 m/min at 15% grade) with 85Sr- and 141Ce-labeled 15-microns microspheres. Zabicipril ingestion induced 50 and 65% inhibition of plasma ACE activity in the low- and high-dose group, respectively (P < 0.001). ACE inhibition did not affect body weight, blood pressure, or heart rate of the rats during exercise. However, BFs to the total hindlimb were 44 and 36% higher (P < 0.001) in zabicipril-treated animals than in the zero-dose controls (approximately 45 ml.min-1 x 100 g-1). Furthermore, BFs to the proximal hindlimb, distal hindlimb, and gastrocnemius-plantaris-soleus group were 33-44% greater in drug-treated than in control animals (P < 0.025). Higher speed (25 m/min) failed to further increase muscle BF; therefore peak BFs were likely achieved. These results indicate that collateral-dependent BF was improved by ACE inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)