This chapter discusses the molecular mechanisms of nitric oxide (NO) signaling in vascular damage. It emphasizes the promising findings in the field of NO and vascular regeneration. NO controls vasorelaxation, endothelial regeneration, inhibition of platelet adhesion, and leukocyte chemotaxis. NO regulates not only vascular function but also many levels of parenchymal function in organs like the kidney, liver, brain, and lung. The modulation of NO availability by increased release or decreased degradation should be done in a spatially specific manner that would correspond to areas in which a specific isoform plays a regulatory role. Its central position in the regulation of organ physiology and molecular signaling generates the impetus to augment its levels in an attempt to interfere with the pathophysiological cascade that leads to tissue dysfunction and destruction. NO deficiency, critical in the development of atherosclerosis and renovascular diseases, occurs through reduced expression and activity of NO synthase, decreased levels or impaired utilization of L-arginine, and enhanced degradation of NO by oxidation-sensitive mechanisms. Genetic manipulation of NO synthase provides important insights into the pathogenic pathway of vascular diseases. Results from pre-clinical and clinical studies suggest that modulation of oxidation-sensitive mechanisms and augmentation of NO production through the administration of L-arginine and antioxidants improve the neovascularization following bone marrow cell therapy or gene therapy. Moreover, nitrite infusion represents a promising NO-generating approach that offers the potential to modulate vascular function during ischemia.
|Original language||English (US)|
|Title of host publication||Nitric Oxide|
|Number of pages||44|
|State||Published - Jan 1 2010|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)