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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Pulmonary Artery / enzymology*
  • Pulmonary Veins / enzymology*
  • Signal Transduction / physiology*
  • Vasoconstriction / physiology*
  • rho-Associated Kinases / physiology*
  • rhoA GTP-Binding Protein / physiology


  • rho-Associated Kinases
  • rhoA GTP-Binding Protein