The role of nitric oxide in the post-ischemic revascularization process

Abstract

Following arterial occlusion, blood vessels respond by sprouting new capillaries (i.e. angiogenesis) and by growing and remodelling pre-existing arterioles into physiologically relevant arteries (i.e. arteriogenesis). The importance of nitric oxide (NO) in ischemia-induced angiogenesis is supported by 4 main findings: (i) the ischemic limb shows an increase in endothelial nitric oxide synthase (eNOS) mRNA, protein expression and NO synthesis; (ii) the absence of the NO pathway (by either pharmacological inhibition or gene disruption of eNOS) abolishes ischemia-induced angiogenesis; (iii) supplementation of NO by the use of exogenous sources restores ischemia-induced angiogenesis; and (iv) cardiovascular diseases associated with decreased NO synthesis show impaired ischemia-induced angiogenesis. Thus, impairment of the NO metabolic pathway could be one of the main contributing factors for the development of peripheral arterial occlusive disease. The restoration of normal NO levels in diseased arteries is therefore a major therapeutic goal; this could be achieved by supplementation with exogenous NO or by strategies designed to increase the concentration of endogenous NO.