Reactive oxygen species and RhoA signaling in vascular smooth muscle: role in chronic hypoxia-induced pulmonary hypertension

Thomas C Resta, Bradley Randal Scott Broughton, Nikki L Jernigan

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

23 Citations (Scopus)

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.
Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
EditorsJ X-J Yuan, J P T Ward
Place of PublicationUSA
PublisherHumana Press
Pages355 - 374
Number of pages20
Edition661
ISBN (Print)0065-2598
DOIs
Publication statusPublished - 2010

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