Selective Activation of ROCK2 Isoform Contributes to Vasomotor Regulation of Retinal Arterioles

Rho kinase (ROCK) and the vasoconstrictor endothelin‐1 (ET‐1) are involved in the vasomotor regulation of various tissues, including the eyes, but their interrelationship remains unknown. Herein, we examined ROCK isoform expression and its role in myogenic tone and ET‐1‐mediated constriction of isolated/pressurized porcine retinal arterioles (~70 μm). Immunohistochemical and immunoblotting analysis demonstrated an 8‐fold greater ROCK2 than ROCK1 expression in both arterioles and neural retina and a predominant ROCK2 expression in arteriolar smooth muscle cells. Retinal tissue and arterioles both express the ET‐1 precursor pre‐pro‐ET‐1. The non‐selective ROCK inhibitor H‐1152 (3 μM) significantly inhibited myogenic tone by 94±0.4% and fully reversed vasoconstriction elicited by ET‐1 (1 nM). Similarly, myogenic tone and ET‐1‐mediated vasoconstriction were unattainable after siRNA knockdown of ROCK2, but not ROCK1. Taken together, our results suggest a major role of ROCK2 in maintaining myogenic tone and the vasoconstriction to ET‐1 in retinal arterioles. ROCK2 likely mediates physiologic and pathophysiologic responses to endogenously released ET‐1. Retina Research Foundation (LK) and NIH EY018420 (TWH)