Rho Kinase-mediated Coronary Arteriolar Constriction to Endothelin-1: Mechanistic Implications for Cardiac Syndrome X

Rho kinase (ROCK) has been implicated in mediating diverse biological functions of various cells. Accumulating evidencehas suggested that abnormal activation of ROCK contributes to the development of cardiovascular disease. Theelevation of endothelin-1, the most potent endogenous vasoconstrictor, is also known to be associated with numerouscardiovascular disorders. Recent reports suggest that the constriction of the coronary microvasculature to endothelin-1is mediated by the activation of ROCK signaling. In this article, we provide an overview on the ROCK and endothelin-1vascular biology in relation to the control of vasomotor activity and speculate on their contributions to local myocardialischemia and cardiac syndrome X. Although the underlying cellular and molecular mechanisms involved in exertingendothelin-1/ROCK regulation of coronary microvascular function remain elusive, the development of specific and selectiveROCK inhibitors appears to have therapeutic potential in cardiovascular disease treatment.