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

J Anesth. 2015 Apr;29(2):186-90. doi: 10.1007/s00540-014-1903-x. Epub 2014 Aug 24.

Abstract

Purpose: 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.

Method: 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) mol l(-1); n = 7) dissolved in artificial cerebrospinal fluid for 7 min each. We measured the diameters of pial vessels, mean arterial pressure (MAP), heart rate (HR), and rectal temperature at 7 min after application of each Y-27632 concentration.

Results: 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) mol l(-1) did not produce any significant change in pial arterioles. Topical application of Y-27632 at 10(-6) and 10(-5) mol l(-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.

Conclusion: 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) mol l(-1). Y-27632 is a potent cerebral pial arteriolar dilator but is not a venular dilator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology*
  • Animals
  • Arterial Pressure / drug effects
  • Arterioles / drug effects
  • Body Temperature / drug effects
  • Capillaries / drug effects*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • Microcirculation / drug effects
  • Pia Mater / blood supply*
  • Pia Mater / drug effects*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology*
  • Rabbits
  • Vasodilation / drug effects
  • Venules / drug effects
  • rho-Associated Kinases / antagonists & inhibitors*

Substances

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