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Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

  1. Ayako Makino1,
  2. Amy L. Firth2,
  3. Jason X.-J. Yuan1

Published Online: 1 JUL 2011

DOI: 10.1002/cphy.c100023

Comprehensive Physiology

Comprehensive Physiology

How to Cite

Makino, A., Firth, A. L. and Yuan, J. X.-J. 2011. Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling. Comprehensive Physiology. 1:1555–1602.

Author Information

  1. 1

    Department of Medicine, The University of Illinois at Chicago, Chicago, Illinois

  2. 2

    The Salk Institute for Biological Studies, La Jolla, California

Publication History

  1. Published Online: 1 JUL 2011


The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease. © 2011 American Physiological Society. Compr Physiol 1:1555-1602, 2011.