Direct effects of Rho-kinase inhibitor on pial microvessels in rabbits.

Abstract

Rho-kinase inhibitor is widely used for prevention of cerebral vascular spasm. However, the cerebral pial vascular action of Rho-kinase inhibitor has not been investigated. We therefore evaluated the direct effects of Y-27632, a Rho-kinase inhibitor, on pial microvessels. Experiments were performed on anesthetized rabbits. A closed cranial window was used to visualize the pial microcirculation. After baseline hemodynamic and pial vascular measurements, the cranial window was superfused with four increasing concentrations of Y-27632 (10(-9), 10(-7), 10(-6), 10(-5) moll(-1); n=7) dissolved in artificial cerebrospinal fluid for 7min each. We measured the diameters of pial vessels, mean arterial pressure (MAP), heart rate (HR), and rectal temperature at 7min after application of each Y-27632 concentration. MAP, HR, rectal temperature, arterial pH, PaCO2, PaO2, and plasma Na(+), K(+) and glucose concentrations did not change significantly during the experimental period. Y-27632 at 10(-9) to 10(-7) moll(-1) did not produce any significant change in pial arterioles. Topical application of Y-27632 at 10(-6) and 10(-5) moll(-1) produced pial large (8.4±5.7 and 19.8±12.7%) and small (10.1±8.5 and 18.1±12.3%) arterioles dilation. However, Y-27632 did not produce any change in pial large and small venules. We evaluated the direct effects of Y-27632 on pial microvessels. Y-27632 dilates only pial arterioles in a concentration-dependent manner, and most at a concentration of 10(-5) moll(-1). Y-27632 is a potent cerebral pial arteriolar dilator but is not a venular dilator.