Comparative effects of nitric oxide dependent and independent vasodilation on impaired hindlimb revascularization in eNOS-/- mice

Manuel Martínez-Ruiz, Hilda Vargas-Robles, Amelia Rios, Daniel Sánchez, Bruno Escalante

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Ischemia due to vascular occlusion induces vasodilation as an initial response, followed by arteriogenesis or angiogenesis. Vasodilation through nitric oxide (NO) independent and dependent mechanisms may be sufficient to restore the altered neovascularization in pathological situations where the NO is altered. Using a posterior limb claudication model to evaluate ischemia-induced revascularization in eNOS−/− mice, we compared the effects of sodium nitrite, a NO-dependent vasodilator, and prazocin, an alpha-adrenergic blocker and NO-independent vasodilator, on hindlimb revascularization. We evaluated the blood flow of the hindlimbs, NO and nitrites metabolites, the expression of tissue endothelial cell markers and proangiogenic factors, as well as the gait locomotion. Our results suggest that the use of a peripheral vasodilator can substitute the initial absence of NO as an endogenous vasodilator. However, final resolution of the ischemic process requires a NO-mediated pathway, which through changes in vascular hemodynamics, promotes the generation of angiogenic messengers facilitating the functional recovery of the damaged limb.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalCanadian Journal of Physiology and Pharmacology
Issue number5
Publication statusPublished - 1 Jan 2019


All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

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