Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis.
There is a complex pathophysiologic scenario involving nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and the development of atherosclerosis and unstable atheroma. Endothelial damage induced by atherosclerosis leads to the reduction in bioactivity of eNOS with subsequent impaired release of NO. An important mechanism is local enhanced degradation of NO by increased generation of reactive oxygen species and other free radicals, with subsequent cascade of oxidation-sensitive mechanisms in the arterial wall. Novel molecular approaches have resulted in the development of new strains of mice lacking eNOS. These experimental models will help to understand how to implement NO-based therapies against atherosclerosis. L-arginine, the precursor of NO, has demonstrated beneficial effects in atherosclerosis and disturbed shear stress. The target or goal for new drugs should be the complete restoration of NO-mediated signaling pathways in atherosclerotic arteries.
Ignarro
Louis J
LJ
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, 23-305 Center for Health Sciences, Los Angeles, CA 90095, USA. lignarro@mednet.ucla.edu
Napoli
Claudio
C
D001120:Arginine / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D023421:Models, Animal; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III