Cerebral ATP-Sensitive Potassium Channels During Acute Reduction of Carotid Blood Flow

Abstract The ATP-sensitive potassium channels (K ATP ) are activated either by a decrease in intracellular ATP content or by a lowering of the ATP-ADP ratio such as during stroke. We studied the role of cerebral K ATP on arterial pressure during acute reduction of cerebral blood flow in 12-week-old male Wistar rats anesthetized with urethane by recording arterial pressure and heart rate continuously. After bilateral ligation of the common carotid arteries, glibenclamide, a specific blocker of K ATP , was injected intracerebroventricularly into the cerebral lateral ventricle. Glibenclamide elicited a sustained vasopressor response in a dose-dependent manner in rats with bilateral carotid artery ligation (10 nmol, +15±2 mm Hg; 1 nmol, +5±1 mm Hg, P 1 -adrenoceptor antagonist, did not affect the pressor response of intracerebroventricular glibenclamide. To investigate the vasopressor mechanism further, we measured plasma and pituitary concentrations of arginine vasopressin and determined the effects of vasopressin receptor antagonists. The intracerebroventricular injections of glibenclamide significantly increased the plasma concentration of vasopressin ( P P 1 receptor antagonist OPC-21268 abolished the vasopressor response to intracerebroventricular glibenclamide (+16±2 versus +1±1 mm Hg, P ATP in the brain may inhibit an excess rise in arterial pressure in part by decreasing the release of vasopressin from the pituitary during bilateral carotid artery ligation.