title: Ca2+ channels and chronic hypoxia.
abstract: Many chronic lung diseases are associated with prolonged exposure to alveolar hypoxia, resulting in the development of pulmonary hypertension. While the exact mechanisms underlying the pathogenesis of hypoxic pulmonary hypertension remain poorly understood, a key role for changes in Ca2+ homeostasis has emerged. Intracellular Ca2+ concentration controls a variety of pulmonary vascular cell functions, including contraction, gene expression, growth, barrier function and synthesis of vasoactive substances. Several studies indicate that prolonged exposure to hypoxia causes alterations in the expression and activity of several Ca2+ handling pathways in pulmonary arterial smooth muscle cells. In contrast, the effect of chronic hypoxia on Ca2+ homeostasis in pulmonary arterial endothelial cells is relatively unexplored. In this review, we discuss data from our laboratory and others describing the effects of prolonged hypoxia on pulmonary vascular smooth muscle and endothelial cell Ca2+ homeostasis and the various Ca2+ channels and handling pathways involved in these responses. We will also highlight future directions of investigation that might improve our understanding of the response of pulmonary vascular cells to chronic hypoxia.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA. shimoda1@welch.jhu.edu
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Shimoda
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: J T
authors.initials: JT
authors.lastname: Sylvester
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002908:Chronic Disease; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology
chemical_list: D015220:Calcium Channels