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

Am J Physiol Heart Circ Physiol. 2001 Dec;281(6):H2528-38. doi: 10.1152/ajpheart.2001.281.6.H2528.

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(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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arterioles / physiology
  • Capillaries / physiology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Hindlimb / blood supply
  • Ischemia / physiopathology*
  • Kidney / blood supply
  • Male
  • Muscle, Skeletal / blood supply
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Peripheral Vascular Diseases / physiopathology
  • Physical Conditioning, Animal / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / physiology

Substances

  • Enzyme Inhibitors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester