Arteriogenesis and angiogenesis in rat ischemic hindlimb: role of nitric oxide.
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(omega)-nitro-L-arginine methyl ester (L-NAME; 65-70 mg x kg(-1) x day(-1), via drinking water) were divided into sedentary or exercise-trained subgroups. After approximately 3 wk, L-NAME treatment had elevated preexercise mean arterial pressure approximately 39-58%, confirming NO synthesis inhibition. The training program (treadmill exercise twice per day, 20-25 m/min, 15% grade, approximately 18 days) increased collateral-dependent blood flow to the distal hindlimb, with the greatest increase (approximately 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 by L-NAME. Thus arteriogenesis and angiogenesis appear to differ in their requirement for NO.
Lloyd
P G
PG
Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211-5120, USA.
Yang
H T
HT
Terjung
R L
RL
D000818:Animals; D001160:Arterioles / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester