Reactive oxygen species and RhoA signaling in vascular smooth muscle: role in chronic hypoxia-induced pulmonary hypertension.
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.
Resta
Thomas C
TC
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA. Tresta@salud.unm.edu
Broughton
Brad R S
BR
Jernigan
Nikki L
NL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011651:Pulmonary Artery / Q000033:anatomy & histology / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D017382:Reactive Oxygen Species; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D002118:Calcium