title: Effects of potassium channel inhibitors on the relaxation induced by the nitric oxide donor diethylamine nitric oxide in isolated human cerebral arteries.
abstract: OBJECTIVE
  The goal of this study was to investigate whether K+ channels are involved in nitric oxide (NO)-induced relaxation of isolated human cerebral arteries.
  
  
  METHODS
  Successive concentration-response curves relating to the use of the NO donor diethylamine NO (DEA/NO) were established in the absence and presence of different K+ channel inhibitors after mounting human cerebral arteries onto a wire myograph. The arteries were obtained from macroscopically intact tissue that had been removed during brain tumor operations. A high K+ concentration partially inhibited the relaxant effects of DEA/NO. Different K+ channel inhibitors (tetraethylammonium [TEA], 10(-3) M; charybdotoxin, 10(-7) M; glibenclamide, 10(-6) M; 4-aminopyridine [4-AP], 10(-3) M; BaCl2, 5 x 10(-5) M; and apamin, 10(-6) M) alone failed to affect the responses to DEA/NO. However, a combination of TEA, glibenclamide, 4-AP, and BaCl2 partially blocked the relaxant effects of DEA/NO. In addition, the effects of DEA/NO were inhibited by the thromboxane A2 analog U46619 (3 x 10(-7) M).
  
  
  CONCLUSIONS
  Inhibitors of the large-conductance or small-conductance Ca++-activated K+ channels, the adenosine triphosphate-sensitive K+ channels, and the delayed-rectifier or inward-rectifier K+ channels failed to alter the effects of DEA/NO when only one K+ channel blocker was used. However, a regimen of a combination of K+ channel blockers that possess selectivity for different channels demonstrated that different K+ channel types are involved; these channels may function in a redundant manner and compensate for each other. Selective thromboxane A2 agonists are capable of inhibiting the relaxant response to the NO donor.
authors: Department of Neurosurgery, University of Kiel, Germany. hempelmannr@nch.uni-kiel.de
authors: R G
authors: RG
authors: Hempelmann
authors: J
authors: J
authors: Seebeck
authors: A
authors: A
authors: Ziegler
authors: H M
authors: HM
authors: Mehdorn
mesh_terms: D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004048:Diethylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004048:Diethylamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009569:Nitric Oxide; C034281:diethylamine