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

•We propose a link between hemodynamics and Rho kinase activity in the endothelium.•Cross talk between nitric oxide and Rho kinase signaling defines vascular functions.•We review the promise of Rho-kinase as a therapeutic target in vascular diseases.

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.