Role of the RhoA/Rho-kinase pathway in the regulation of pulmonary vasoconstrictor function.
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.
Nossaman
Bobby D
BD
Department of Anesthesiology, Critical Care Section, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA.
Nossaman
Vaughn E
VE
Murthy
Subramanyam N
SN
Kadowitz
Philip J
PJ
D000818:Animals; D006801:Humans; D011651:Pulmonary Artery / Q000201:enzymology*; D011667:Pulmonary Veins / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein