title: Global ischemia impairs ATP-sensitive K+ channel function in cerebral arterioles in piglets.
abstract: OBJECTIVE
  Indirect evidence from studies in which calcitonin gene-related peptide was used indicates that anoxic stress suppresses functioning of cerebral vascular ATP-sensitive K+ channels. The purpose of this study was to directly examine effects of total global ischemia on cerebral arteriolar dilator responses to activators of ATP-sensitive K+ channels.
  
  
  METHODS
  We measured pial arteriolar diameters in anesthetized piglets using a closed cranial window and intravital microscopy. Baseline diameters were approximately 100 microns. Arteriolar responses to aprikalim (10(-8) and 10(-6) mol/L), a pharmacological activator of ATP-sensitive K+ channels, and iloprost (0.1 and 1 microgram/mL), a physiological activator of these channels, were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure.
  
  
  RESULTS
  Before ischemia, aprikalim dilated cerebral arterioles by 7 +/- 2% at 10(-8) mol/L and by 25 +/- 4% at 10(-6) mol/L (n = 5). At 1 hour after ischemia, aprikalim did not cause significant dilation at either dose (3 +/- 2% at 10(-8) mol/L and 7 +/- 4% at 10(-6) mol/L; P < .05 compared with corresponding preischemic response). Arteriolar dilation returned toward normal values at 2 and 4 hours. Similar results were found with iloprost. Furthermore, prior treatment with indomethacin (5 mg/kg) preserved normal arteriolar dilation to aprikalim and iloprost after ischemia. In contrast, arteriolar dilator responses to prostaglandin E2 were intact after ischemia.
  
  
  CONCLUSIONS
  Ischemia transiently eliminates cerebral arteriolar dilation to activation of ATP-sensitive K+ channels; arteriolar responses are suppressed at 1 hour and return toward normal over 2 to 4 hours. In addition, reduced responsiveness can be prevented by prior treatment with indomethacin.
authors.affiliation: Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA.
authors.forename: F
authors.initials: F
authors.lastname: Bari
authors.forename: T M
authors.initials: TM
authors.lastname: Louis
authors.forename: W
authors.initials: W
authors.lastname: Meng
authors.forename: D W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007223:Infant; D008297:Male; D010847:Picolines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D011714:Pyrans / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; D014665:Vasodilator Agents; C061043:aprikalim; D000255:Adenosine Triphosphate; D016285:Iloprost; D015232:Dinoprostone