title: Nitric oxide and atherosclerosis.
abstract: Endothelial dysfunction has been shown in a wide range of vascular disorders including atherosclerosis and related diseases. Here, we examine and address the complex relationship among nitric oxide (NO)-mediated pathways and atherogenesis. In view of the numerous pathophysiological actions of NO, abnormalities could potentially occur at many sites: (a) impairment of membrane receptors in the arterial wall that interact with agonists or physiological stimuli capable of generating NO; (b) reduced concentrations or impaired utilization of l-arginine; (c) reduction in concentration or activity both of inducible and endothelial NO synthase; (d) impaired release of NO from the atherosclerotic damaged endothelium; (e) impaired NO diffusion from endothelium to vascular smooth muscle cells followed by decreased sensitivity to its vasodilator action; (f) local enhanced degradation of NO by increased generation of free radicals and/or oxidation-sensitive mechanisms; and (g) impaired interaction of NO with guanylate cyclase and consequent limitation of cyclic GMP production. Therefore, one target for new drugs should be the preservation or restoration of NO-mediated signaling pathways in arteries. Such novel therapeutic strategies may include administration of l-arginine/antioxidants and gene-transfer approaches.
authors: Department of Medicine, Federico II University of Naples, Naples, Italy. claunap@tin.it
authors: C
authors: C
authors: Napoli
authors: L J
authors: LJ
authors: Ignarro
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D001120:Arginine / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D001120:Arginine