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- Title
Role of the RhoA/Rho-kinase pathway in the regulation of pulmonary vasoconstrictor function.
- Authors
Nossaman, Bobby D.; Nossaman, Vaughn E.; Murthy, Subramanyam N.; Kadowitz, Philip J.
- 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.
- Subjects
VASOCONSTRICTORS; HYPERTENSION; SMOOTH muscle; MUSCLE contraction; CARRIER proteins
- Publication
Canadian Journal of Physiology & Pharmacology, 2010, Vol 88, Issue 1, p1
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/Y09-092