Journal
PHARMACOLOGY
Volume 79, Issue 2, Pages 65-75Publisher
KARGER
DOI: 10.1159/000097754
Keywords
K-V channels; Rho kinase; pulmonary arterial hypertension; vascular tone; protein kinase C; signaling pathways
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Pulmonary vasoconstriction is believed to be an early component of pulmonary arterial hypertension. Intracellular calcium concentration ([Ca2+](i)) is a major trigger for pulmonary vasoconstriction; however, it is now well known that contractions and relaxations may also be elicited through Ca2+-independent mechanisms. A variety of intracellular protein kinases and cyclic nucleotides have been identified as key determinants in controlling pulmonary vascular tone. Herein, we provide an overview of the main signaling pathways, which include protein kinase C, Rho kinases and cyclic nucleotides (cAMP and cGMP). This review also focuses on the role of store-operated Ca2+ channels and voltage-gated K+ channels, which are currently considered especially attractive in the pulmonary circulation and may represent new targets in the treatment of pulmonary arterial hypertension. Copyright (c) 2007 S. Karger AG, Basel.
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