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

Objective: 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. Design: Prospective, randomized, experimental study with repeated measures. Setting: Investigational animal laboratory. Subjects: Twenty-four cats. Interventions: Animals were anesthetized with pentobarbital. The cranial window technique, combined with microscopic video recording, was used to measure small (50-100 μm) and large (100-200 μm) pial arteriolar diameter in an experiment. Animals were assigned randomly to either a normothermic (37°C) or a hypothermic (33°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. Measurements and Main Results: 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. Conclusions: 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.