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Current Drug Discovery Technologies

Eiditor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension

Author(s): Bobby D. Nossaman and Philip J. Kadowitz

Volume 6 , Issue 1 , 2009

Page: [59 - 71] Pages: 13

DOI: 10.2174/157016309787581057

Price: $58

Abstract

The small GTP-binding protein, RhoA, and its downstream effector protein, rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of rho-kinase is involved in the development of increased vascular tone, endothelial dysfunction, inflammation, and restenosis; and that the inhibition of rho-kinase has been shown to have a beneficial effect in a variety of cardiovascular disorders. It is our hypothesis that rho-kinase inhibitors promote vasodilation independent of the mechanism that increases vasoconstrictor tone and moreover, the RhoA/rho-kinase pathway has a role in the regulation of smooth muscle tone under physiological conditions. The objective of this review is to improve our current understanding of the role of RhoA/rho-kinase pathway in the regulation of vasoconstrictor tone and the use of rho-kinase inhibitors in the treatment of cardiovascular disorders with an emphasis on pulmonary hypertension.

Keywords: Intracellular signaling peptides and proteins, protein kinases, RhoA/rho-kinase pathway, muscle, smooth, vascular, pulmonary hypertension, pulmonary vascular bed, systemic vascular bed, signal transduction, inhibitors/pharmacology, cardiovascular diseases, fasudil, HA-1077, Y-27632


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