Reactive oxygen species signaling in pulmonary vascular smooth muscle.
In recent years, it has become evident that reactive oxygen species (ROS) play a critical role in the regulation of several physiological and pathophysiological processes. Herein we review the main sources, targets and pathophysiological roles of ROS in pulmonary vascular smooth muscle. Mitochondria and NADPH oxidases represent the major sources of ROS in vascular cells. In addition, ROS can be produced by different pathways of arachidonic acid metabolism, endothelial NO synthase (eNOS) and xantine oxidase. There is increasing evidence for the role of ROS, specially hydrogen peroxide, as signaling moieties to induce increase in intracellular calcium concentration ([Ca2+]i) and contraction in pulmonary artery smooth muscle cells (PASMC) through the modulation of a variety of targets, such as Rho kinases (ROCK), protein kinase C (PKC), voltage-gated potassium K+ (Kv) channels and ryanodine receptors (RyR). Thus, an increase in ROS has been reported to contribute to the responses induced by different vasoconstrictor stimuli, including hypoxia. Finally, results from recent studies highlighting the involvement of ROS in the development of pulmonary hypertension are discussed in the present paper.
Perez-Vizcaino
Francisco
F
Department of Pharmacology, School of Medicine, University Complutense of Madrid and Ciber Enfermedades Respiratorias (Ciberes), 28040 Madrid, Spain. fperez@med.ucm.es
Cogolludo
Angel
A
Moreno
Laura
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D019255:NADPH Oxidases / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D002118:Calcium