• Mehran Mandegar and Jason X J Yuan.
• Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, 200 West Arbor Drive, San Diego, CA 92103-8382, USA.
• Vascul. Pharmacol. 2002 Jan 1; 38 (1): 25-33.

AbstractPulmonary hypertension is a hemodynamic abnormality that is common to a variety of conditions. In obliterative pulmonary hypertension, vascular remodeling leads to an obliterative process involving the small muscular pulmonary arteries, thereby increasing pulmonary vascular resistance (PVR) and the pulmonary artery pressure (PAP). This process can be triggered by a defect in the function of K+ channels or by alveolar hypoxia. In fact, hypoxia has been shown to selectively inhibit the function and expression of voltage-gated K+ (KV) channels in pulmonary arterial smooth muscle cells (SMCs). K+ channel dysfunction, therefore, plays an important role in the development of pulmonary hypertension. Activity of K+ channels regulates the membrane potential (Em) of SMCs, which in turn regulates cytoplasmic free Ca2+ concentration ([Ca2+]cyt). Depolarization of the Em leads to an elevated [Ca2+]cyt by opening voltage-dependent Ca2+ channels. Elevated [Ca2+]cyt is implicated in stimulating vascular SMC proliferation and inducing vasomotor tone, and hence, vasoconstriction. Vasoconstriction causes elevation of intravascular pressure and elastic stretch of the SMCs, both of which have been shown to play a role in pulmonary arterial cellular growth and synthetic activity, creating a vicious cycle of cellular hypertrophy, proliferation, and vascular remodeling. Dysfunction of K+ channels has also been linked to decreased apoptosis in pulmonary arterial SMCs, a condition that contributes further to the medial hypertrophy of the arterial walls and vascular remodeling. The goal of this article is to review the current understanding of the function of K+ channels and their contribution to the pathophysiology and cellular mechanisms involved in the development of pulmonary hypertension.

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