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Reactive Oxygen Species and RhoA Signaling in Vascular Smooth Muscle: Role in Chronic Hypoxia-Induced Pulmonary Hypertension

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Membrane Receptors, Channels and Transporters in Pulmonary Circulation

Part of the book series: Advances in Experimental Medicine and Biology ((volume 661))

Abstract

Increases in myofilament Ca2+ sensitivity resulting from stimulation of RhoA and Rho kinase represent a primary mechanism of vasoconstriction and associated pulmonary hypertension resulting from chronic hypoxia (CH). This chapter summarizes recent advances in the understanding of RhoA/Rho kinase signaling mechanisms in pulmonary vascular smooth muscle (VSM) that increase the sensitivity of the contractile apparatus to Ca2+ and contribute to vasoconstriction in this setting. Such advances include the discovery of myogenic tone in small pulmonary arteries from CH rats that contributes to vasoconstriction through a mechanism inherent to the VSM, dependent on Rho kinase-induced Ca2+ sensitization but independent of L-type voltage-gated Ca2+ channels. Additional studies have revealed an important contribution of superoxide anion (O2-)-induced RhoA activation to both receptor-mediated and membrane depolarization-induced myofilament Ca2+ sensitization in hypertensive pulmonary arteries. Xanthine oxidase and NADPH oxidase isoforms are potential sources of O2- that mediate RhoA-dependent vasoconstriction and associated pulmonary hypertension.

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Authors and Affiliations

  1. Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA

    Thomas C. Resta, Brad R. S. Broughton & Nikki L. Jernigan

  2. Department of Pharmacology, Monash University, Clayton, 3800, VIC, Australia

    Brad R. S. Broughton

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  1. Thomas C. Resta
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  2. Brad R. S. Broughton
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  3. Nikki L. Jernigan
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Correspondence to Thomas C. Resta .

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Editors and Affiliations

  1. Departments of Medicine and Pharmacology, University of Illinois at Chicago, Chicago, 60612, USA

    Jason X. -J. Yuan

  2. Guy’s Hospital Campus, Dept. Physiology, King’s College London, London, SE1 1UL, United Kingdom

    Jeremy P. T. Ward

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Resta, T.C., Broughton, B.R.S., Jernigan, N.L. (2010). Reactive Oxygen Species and RhoA Signaling in Vascular Smooth Muscle: Role in Chronic Hypoxia-Induced Pulmonary Hypertension. In: Yuan, JJ., Ward, J. (eds) Membrane Receptors, Channels and Transporters in Pulmonary Circulation. Advances in Experimental Medicine and Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-500-2_23

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