Effect of mild hypothermia on nicorandil-induced vasodilation of pial arterioles in cats

Abstract

Nicorandil is characterized as hybrid between nitrates and potassium channel activators. Recent evidence suggested that mild hypothermia may alter cerebral vasodilation induced by a nitrate agent and potassium channel opener. However, the effect of mild hypothermia on nicorandil-induced vasodilation is not known. The present study was conducted to investigate whether mild hypothermia could alter nicorandil-induced cerebral vasodilation. In addition, the effects of mild hypothermia on cerebral vasodilation induced by nitroglycerin, a nitrate agent, and cromakalim, a selective adenosine 5'-triphosphate-sensitive potassium channel opener, were assessed in the same model. Prospective, randomized, experimental study with repeated measures. Investigational animal laboratory. Twenty-four cats. Animals were anesthetized with pentobarbital. The cranial window technique, combined with microscopic video recording, was used to measure small (50-100 microm) and large (100-200 microm) pial arteriolar diameter in an experiment. Animals were assigned randomly to either a normothermic (37 degrees C) or a hypothermic (33 degrees C) group. Nicorandil, nitroglycerin, or cromakalim at concentrations of 10(-8), 10(-6), or 10(-4) mol/L was applied topically in the cranial window, and the diameter of pial arterioles was measured. Topical administration of nicorandil, nitroglycerin, and cromakalim significantly dilated both small and large pial arterioles in a dose-dependent manner during normothermia. Nicorandil-induced vasodilation of either large or small pial arterioles was not affected by hypothermia. However, hypothermia significantly attenuated nitroglycerine-induced vasodilation in both large and small pial arterioles and enhanced cromakalim-induced vasodilation in both large and small pial arterioles. Nicorandil-induced vasodilation of cerebral pial arterioles was not affected by mild hypothermia. By contrast, mild hypothermia significantly attenuated nitroglycerin-induced vasodilation and enhanced cromakalim-induced vasodilation.