Role Of Nitric Oxide And Nitric Oxide Synthase In The Development Of Hypoxic Pulmonary Hypertension And The'Double-edged Sword'Effect Of Nitric Oxide

Nitric oxide (NO) is an important cellular messenger molecule that has been implicated in a wide range of physiological and pathophysiological actions in the cardiovascular, immune and nervous systems. NO has multiple biological roles in regulation of vascular tone, platelet aggregation, leukocyte adhesion, neurotransimission and cytostatic/cytotoxic actions. NO is synthesized by nitric oxide synthase (NOS) that catalyzes the conversion of L-arginine to L-citrulline in the presence of O₂ and NADPH. NOS is the sole and keyenzyme responsible for NO synthesis. Endothelial-derived NO (EDNO) produced by endothelial nitric oxide synthase (eNOS) acts on soluble guanylyl cyclase in the vascular smooth muscle to stimulate guanosine 3',5'-cyclic monophosphate (cGMP) formation, which leads to vasodilation. NO plays an important regulatory role in the homeostasis of cardiovascular functions and in the pathogenesis of cardiovascular diseases. Hypoxic pulmonary hypertension (HPH) is a common complication of many cardiopulmonary diseases. Pulmonary vasoconstriction and vascular remodeling are two important characteristics of hypoxic pulmonary hypertension. Role of NO and NOS in the normal and hypertensive pulmonary vasculature remains to...