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Journal Article
Review
The Nitric Oxide Pathway in Pulmonary Vascular Disease.
American Journal of Cardiology 2017 October 16
Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L-arginine in pulmonary vascular endothelial cells by nitric oxide synthase and diffuses to adjacent vascular smooth muscle cells where it activates soluble guanylyl cyclase. This enzyme converts GTP to cGMP which activates cGMP dependent protein kinase leading to a series of events that decrease intracellular calcium and reduce vascular muscle tone. Nitric oxide is an important mediator of pulmonary vascular tone and vascular remodeling. A number of studies suggest that the bioavailability of nitric oxide is reduced in patients with pulmonary vascular disease and that augmentation of the nitric oxide/cGMP pathway may be an effective strategy for treatment. Several medications that target nitric oxide/cGMP signaling are now available for the treatment of pulmonary hypertension. This review explores the history of nitiric oxide research, describes the major NO synthetic and signaling pathways and discusses a variety of abnormalities in NO production and metabolism that may contribute to the pathophysiology of pulmonary vascular disease. A summary of the clinical use of presently available medications that target nitric oxide/cGMP signaling in the treatment of pulmonary hypertension is also presented.
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