Rho-kinase as a therapeutic target in vascular diseases: striking nitric oxide signaling

Nitric Oxide. 2014 Dec 1:43:45-54. doi: 10.1016/j.niox.2014.09.002. Epub 2014 Sep 6.

Abstract

Rho GTPases are a globular, monomeric group of small signaling G-protein molecules. Rho-associated protein kinase/Rho-kinase (ROCK) is a downstream effector protein of the Rho GTPase. Rho-kinases are the potential therapeutic targets in the treatment of cardiovascular diseases. Here, we have primarily discussed the intriguing roles of ROCK in cardiovascular health in relation to nitric oxide signaling. Further, we highlighted the biphasic effects of Y-27632, a ROCK inhibitor under shear stress, which acts as an agonist of nitric oxide production in endothelial cells. The biphasic effects of this inhibitor raised the question of safety of the drug usage in treating cardiovascular diseases.

Keywords: Nitric oxide; ROCK inhibitors; Rho-GTPases; Shear stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amides / pharmacology
  • Amides / therapeutic use
  • Drug Delivery Systems
  • Humans
  • Nitric Oxide / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Signal Transduction / drug effects
  • Vascular Diseases / drug therapy
  • Vascular Diseases / enzymology*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism*

Substances

  • Amides
  • Protein Kinase Inhibitors
  • Pyridines
  • Y 27632
  • Nitric Oxide
  • rho-Associated Kinases