title: Angiotensin-converting enzyme inhibition increases exercise tolerance and muscle blood flow in rats with peripheral arterial insufficiency.
abstract: To determine the effect of angiotensin-converting enzyme (ACE) inhibition on exercise tolerance and muscle blood flow (BF) to ischemic limbs, both femoral arteries of male Sprague-Dawley rats (approximately 325 g) were surgically stenosed. Rats were either active (treadmill run, 20 m/min (a) 15% grade, 5 d/wk for 3 wk) or sedentary (limited to cage activity), and assigned to one of three doses of zabicipril at 0.0 (zero), 0.3 (low), and 3.0 (high) mg.kg-1.d-1 administered via food intake (N = 14-15/group). After 3 weeks, the left carotid and caudal arteries were catheterized under anesthesia for BF measurement later in the day. Muscle BF was determined during exercise at two treadmill speeds (20 and 30 m/min) with 85Sr and 141Ce labeled microspheres to ensure a peak BF. Plasma ACE was inhibited 31%, 65% in the low- and high-dose sedentary rats and 75%, 74% in the low- and high-dose active animals, respectively (P < 0.001). Angiotensin-converting enzyme inhibition improved exercise tolerance by 3 weeks, at a low speed (20 m/min) in the sedentary groups (P < 0.025) and in a dose-dependent manner at a higher speed (25 m/min) in the active groups (P < 0.001). Blood pressures and heart rates during running were not different among groups. However, total hindlimb BF, reduced to approximately 33% of normal by femoral stenosis, was increased by ACE inhibition and chronic activity in a dose-dependent manner (P < 0.025). Blood flows to the plantar flexors were most improved (approximately 20-40%; to 124 mL.min-1 x 100 g-1) in the high-dose groups (P < 0.01). The higher run speed did not increase BF above the low speed. Training adaptation, indicated by an enhanced muscle mitochondrial content (P < 0.001), was similar for low- and high-dose active animals. Our results indicate that ACE inhibition improves BF to ischemic muscles and, together with chronic physical activity, improves exercise tolerance. The results from this study support those advocating ACE inhibition in managing appropriate patients with peripheral arterial insufficiency.
authors.affiliation: Department of Physiology, SUNY Health Science Center at Syracuse 13210.
authors.forename: H T
authors.initials: HT
authors.lastname: Yang
authors.forename: R L
authors.initials: RL
authors.lastname: Terjung
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017079:Exercise Tolerance / Q000187:drug effects*; D007511:Ischemia / Q000503:physiopathology*; D009043:Motor Activity; D009132:Muscles / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C065499:zabicipril