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

Abstract

The ATP-sensitive potassium channels (KATP) 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 KATP 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 KATP, 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 in sham-operated control rats. The abdominal sympathetic discharge was not increased significantly enough to explain the pressor mechanism. Similarly, pretreatments with intravenous injections of bunazosin, an alpha 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 < .05) and significantly decreased the pituitary concentration of vasopressin (P < .05) in rats with bilateral carotid artery ligation. Intravenous pretreatment with the vasopressin V1 receptor antagonist OPC-21268 abolished the vasopressor response to intracerebroventricular glibenclamide (+16 +/- 2 versus +1 +/- 1 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

The Mitochondrial KATP Channel Opener BMS-191095 Reduces Neuronal Damage after Transient Focal Cerebral Ischemia in Rats

“…The procedures were approved by the Animal Care and Use Committee of Wake Forest University Health Sciences. BMS-191095 (Bristol-Myers Squibb, Princeton, NJ, USA) was dissolved in dimethyl sulfoxide and 15 mL of the solution was infused into the left lateral ventricle under stereotaxic guidance (AP À0.8 mm, lateral 1.5 mm, and dorsoventral 3.7 mm) as described by Nishimura et al (1995), with some modifications.…”

Opening of Mitochondrial ATP-Sensitive Potassium Channels Is a Trigger of 3-Nitropropionic Acid–Induced Tolerance to Transient Focal Cerebral Ischemia in Rats

“…Group 2 (nϭ16) consisted of rats injected with only saline (sodium chloride 0.9%, IP). In group 3 (nϭ16), animals received glibenclamide (Sigma; 0.1 mg/kg, dissolved in 20 L dimethyl sulfoxide) into the left lateral ventricle under stereotaxic guidance as described by Nishimura et al 19 20 minutes before 3-NPA administration. In group 4 (nϭ16), animals were treated with 5-HD (Sigma; 40 mg/kg, in sodium chloride 0.9% to a concentration of 1 mg/mL, buffered [pH 7.4] with NaOH, IP) 20 minutes before administration of 3-NPA.…”

The Cardiovascular Effects of Central Hydrogen Sulfide Are Related to KATP Channels Activation

“…Glibenclamide was initially dissolved in dimethysulfoxide (DMSO) and diluted with aCSF to the final concentration (the final percentage of DMSO in aCSF is not more than 1 %). The dose of NaHS, SAM, HA and glibenclamide was based on our preliminary experiment and previous studies (Dawe et al 2008, Nishimura et al 1995b, Nishimura et al 1995a, Lin et al 1999. The volume of drug injection was 5 μl, and delivered over a period of approximately 30 s. At the end of each experiment, 5 μl of 2 % Pontamine sky blue solution was injected into LCV to identify the injection area.…”