Novel Agents Targeting Nitric Oxide

Anna-Maria      Kampoli; Dimitris      Tousoulis; Costas      Tentolouris; Christodoulos      Stefanadis

Abstract

Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme nitric oxide synthase (NOS). Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature, may improve the long-term outcome in healthy individuals, high-risk subjects or patients with advanced atherosclerosis. Several therapeutic strategies (including statins, angiotensin converting enzyme inhibitors/angiotensin receptors blockers, insulin sensitizers, antioxidant compounds) are now available, targeting both the synthesis and oxidative inactivation of NO in human vasculature, reversing in that way endothelial dysfunction which is enhanced by the release of nitric oxide from the endothelium.

Keywords: Atherosclerosis, bioavailability, endothelium, nitric oxide, oxidative stress, atherogenesis, endothelial dysfunction, statins, angiotensin converting enzyme inhibitors, angiotensin receptors blockers