Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide.
To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution (N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly (P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 +/- 4 vs. 60 +/- 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially (P < 0.05) shorter in the l-NAME-treated group: 539 +/- 67 vs. 889 +/- 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.
Buckwalter
John B
JB
Department of Anesthesiology and Physiology, Medical College of Wisconsin, and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295, USA. jbuckwal@mcw.edu
Curtis
Valerie C
VC
Valic
Zoran
Z
Ruble
Stephen B
SB
Clifford
Philip S
PS
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D008026:Ligation; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D005082:Physical Exertion / Q000502:physiology; D011817:Rabbits; D012039:Regional Blood Flow / Q000502:physiology
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester