Endogenous vascular remodeling in ischemic skeletal muscle: A role for nitric oxide

John B. Buckwalter, Valerie C. Curtis, Zoran Valic, Stephen B. Ruble, Philip S. Clifford

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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 phenylephtine) 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.

Original languageEnglish
Pages (from-to)935-940
Number of pages6
JournalJournal of Applied Physiology
Volume94
Issue number3
DOIs
StatePublished - 1 Mar 2003
Externally publishedYes

Keywords

  • Angiogenesis
  • Arteriogenesis
  • Blood flow
  • Exercise
  • Rabbits

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