COMPARATIVE EFFECTS OF NITRIC OXIDE DEPENDENT AND INDEPENDENT VASODILATION ON IMPAIRED HINDLIMB REVASCULARIZATION IN NITRIC OXIDE KO(-/-) MICE

Ischemia due to vascular occlusion induces vasodilation as an initial response, followed by arteriogenesis or angiogenesis. Vasodilation through nitric oxide independent and dependent mechanisms may be sufficient to restore the altered neovascularization in pathological situations where the nitric oxide is altered. Using a posterior limb claudication model to evaluate ischemia-induced revascularization in eNOS(-/-) mice, we compared the effects of sodium nitrite, a nitric oxide-dependent vasodilator, and prazocin, an alpha-adrenergic blocker and nitric oxide-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 nitric oxide 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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author