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A Brief Overview of Nitric Oxide and Reactive Oxygen Species Signaling in Hypoxia-Induced Pulmonary Hypertension

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Pulmonary Vasculature Redox Signaling in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 967))

Abstract

Pulmonary hypertension (PH) is characterized by increased vasoconstriction and smooth muscle cell hyperplasia driving pathological vascular remodeling of arterial vessels. In this short review, we discuss the primary source of reactive oxygen species (ROS) and nitric oxide (NO) relevant to PH and the mechanism by which dysregulation of their production contributes to PH. Specifically, hypoxia-induced PH is associated with diminished endothelial nitric oxide synthase (eNOS)-derived NO production and increased production of superoxide (O2 •-) through eNOS uncoupling and defective mitochondrial respiration. This drives the inhibition of the NO/soluble guanylate cyclase (sGC) pathway and activation of the transcription factor hypoxia-inducible factor-1α (HIF-1α) with consequential dysregulation of the pulmonary vasculature. Therapeutics aimed at increasing NO or cGMP bioavailabilities are amenable to hypoxia disease-induced PH. Similarly, strategies targeting HIF-1α are now considered. Overall, pulmonary hypertension including hypoxia-induced PH offers unique opportunities for the rational development of therapeutics centered on modulating redox signaling.

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Acknowledgment

This work was supported in part by National Institutes of health grant K01HL130704 (A. Jaitovich) and American Heart Association grant AHA-16GRNT31280002 (D. Jourd’heuil). Figures were produced using Servier Medical Art (www.servier.com).

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Authors and Affiliations

  1. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA

    Ariel Jaitovich M.D. & David Jourd’heuil Ph.D.

  2. The Division of Pulmonary & Critical Care Medicine, Albany Medical College, Albany, NY, USA

    Ariel Jaitovich M.D.

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Correspondence to Ariel Jaitovich M.D. or David Jourd’heuil Ph.D. .

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  1. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA

    Yong-Xiao Wang

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Jaitovich, A., Jourd’heuil, D. (2017). A Brief Overview of Nitric Oxide and Reactive Oxygen Species Signaling in Hypoxia-Induced Pulmonary Hypertension. In: Wang, YX. (eds) Pulmonary Vasculature Redox Signaling in Health and Disease. Advances in Experimental Medicine and Biology, vol 967. Springer, Cham. https://doi.org/10.1007/978-3-319-63245-2_6

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