Arteriogenesis and angiogenesis in rat ischemic hindlimb: role of nitric oxide

Abstract

Nitric oxide (NO) has been implicated in both collateral expansion (arteriogenesis) and capillary growth (angiogenesis). Exercise training increases collateral-dependent blood flow to tissues at risk of ischemia and enhances capillarity in active skeletal muscle. Exercise also acutely elevates NO. Thus we assessed the role of NO in training-induced arteriogenesis and angiogenesis. These studies utilized a rat model of peripheral vascular disease (bilateral femoral artery ligation). Untreated rats (control) and rats treated with the NO synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME; 65–70 mg · kg−1 · day−1, via drinking water) were divided into sedentary or exercise-trained subgroups. After ∼3 wk, l-NAME treatment had elevated preexercise mean arterial pressure ∼39–58%, confirming NO synthesis inhibition. The training program (treadmill exercise twice per day, 20–25 m/min, 15% grade, ∼18 days) increased collateral-dependent blood flow to the distal hindlimb, with the greatest increase (∼59%) in the calf ( P < 0.001). This increase was inhibited by l-NAME. In contrast, the training-induced increase in muscle capillarity was not blocked byl-NAME. Thus arteriogenesis and angiogenesis appear to differ in their requirement for NO.