title: The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by cyclic adenosine monophosphate.
abstract: OBJECTIVE
  This study was designed to determine whether subarachnoid hemorrhage (SAH) affects the function of the K+ channels responsible for relaxation of canine cerebral arteries in response to adenylate cyclase activation.
  
  
  METHODS
  The effect of K+ channel inhibitors on the arterial relaxation response to forskolin, a direct adenylate cyclase activator, was studied in rings of basilar arteries obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured using the radioimmunoassay technique. In rings with the endothelium removed, relaxation induced by forskolin was not affected by SAH. The relaxation response to forskolin was reduced by charybdotoxin (10(-7) mol/L), a selective Ca++-activated K+ channel inhibitor, in normal arteries and arteries subjected to autologous blood injection. This inhibitory effect of charybdotoxin was significantly greater in arteries involved in SAH than in normal vessels. The relaxation response to forskolin was reduced by 4-aminopyridine (10(-3) mol/L), a delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In contrast, the relaxation response to forskolin was not affected by glyburide (10(-5) mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both normal and SAH arteries. Forskolin (3 x 10(-7) mol/L) produced an approximately 10-fold increase in levels of cAMP. The basal values and increased levels of cAMP detected after stimulation with forskolin were no different in normal arteries and those exposed to SAH.
  
  
  CONCLUSIONS
  These results demonstrate that formation of cAMP and the relaxation response to adenylate cyclase activation are not affected by SAH. However, in diseased arteries, K+ channels assume a more important role in the mediation of relaxation response to forskolin, indicating that SAH may change the mechanisms responsible for vasodilation induced by cAMP.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: H
authors.initials: H
authors.lastname: Onoue
authors.forename: Z S
authors.initials: ZS
authors.lastname: Katusic
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology*; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000503:physiopathology; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D018999:Charybdotoxin; D005576:Colforsin; D015761:4-Aminopyridine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005905:Glyburide