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Can J Physiol Pharmacol. 2010 Jan;88(1):1-8. doi: 10.1139/Y09-092.

Role of the RhoA/Rho-kinase pathway in the regulation of pulmonary vasoconstrictor function.

Author information

1
Department of Anesthesiology, Critical Care Section, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA.

Abstract

Calcium is the major intracellular messenger that triggers smooth muscle contraction. The study of calcium-binding proteins, such as calmodulin and its downstream effectors, reveals critical regulation of smooth muscle contraction by protein kinases and phosphatases. Moreover, the small GTP-binding protein RhoA and its downstream effector protein, Rho-kinase, have been shown to play a novel role in the regulation of smooth muscle contraction. Studies have shown that the activation of Rho-kinase is involved in the development of endothelial dysfunction, inflammation, restenosis, and increased vascular tone in a number of cardiovascular disorders. Because inhibitors of this pathway promote vasodilation independent of the mechanism that increases vasoconstrictor tone, it is our hypothesis that Rho-kinase is constitutively active in regulating vasoconstrictor tone in the pulmonary and systemic vascular beds. Studies in the literature suggest that the RhoA/Rho-kinase pathway has an important role in the pathogenesis of pulmonary hypertension.

PMID:
20130732
DOI:
10.1139/Y09-092
[Indexed for MEDLINE]

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