The role of the RhoA/rho-kinase pathway in pulmonary hypertension.
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.
Nossaman
Bobby D
BD
Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, SL83, New Orleans, Louisiana 70112-2699, USA.
Kadowitz
Philip J
PJ
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein