CEREBRAL ATP-SENSITIVE POTASSIUM CHANNELS DURING ACUTE REDUCTION OF CAROTID BLOOD-FLOW

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 art erial pressure and heart rate continuously. After bilateral ligation o f 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<.01 versus vehicle), but hemodynamic alterations were barely recorded with glibenclamide i n sham-operated control rats. The abdominal sympathetic discharge was not increased significantly enough to explain the presser mechanism. S imilarly, pretreatments with intravenous injections of bunazosin, an a lpha(1)-adrenoceptor antagonist, did not affect the presser response o f intracerebroventricular glibenclamide. To investigate the vasopresso r mechanism further, we measured plasma and pituitary concentrations o f arginine vasopressin and determined the effects of vasopressin recep tor antagonists. The intracerebroventricular injections of glibenclami de significantly increased the plasma concentration of vasopressin (P< .05) and significantly decreased the pituitary concentration of vasopr essin (P<.05) in rats with bilateral carotid artery ligation. Intraven ous pretreatment with the vasopressin V-1 receptor antagonist OPC-2126 8 abolished the vasopressor response to intracerebroventricular gliben clamide (+16+/-2 versus +1+/-1 mm Hg, P<.01). These findings indicate that K-ATP in the brain may inhibit an excess rise in arterial pressur e in part by decreasing the release of vasopressin from the pituitary during bilateral carotid artery ligation.