title: Volatile anaesthetics restore bradykinin and serotonin-induced coronary vasodilation after blocking nitric oxide synthase: lack of anaesthetic effects on KATP channels and prostaglandin pathways.
abstract: OBJECTIVE
  Volatile anaesthetic effects on altering tone after blocking nitric oxide synthase, cyclo-oxygenase-prostaglandin synthase and KATP channel pathways are controversial. We examined in isolated guinea pig hearts whether anaesthetics alter bradykinin and 5-hydroxytryptamine-induced effects on coronary flow and percentage oxygen extraction after blocking these pathways.
  
  
  METHODS
  Before and during exposure to sevoflurane, halothane or isoflurane, hearts were infused with 10-13-10-8 M bradykinin, or 10-8-10-6 M 5-hydroxytryptamine (serotonin), with either L-NAME, indomethacin, or glibenclamide. Bradykinin or 5-hydroxytryptamine alone increased flow and decreased percentage oxygen extraction in a concentration-dependent manner; these effects were largely blocked by L-NAME (nitro-L-arginine methylester), which also decreased basal flow and increased basal percentage oxygen extraction.
  
  
  RESULTS
  The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. Drug-induced increases in flow and decreases in percentage oxygen extraction in the absence or presence of glibenclamide or indomethacin were not altered at either of the two concentrations of anaesthetics.
  
  
  CONCLUSIONS
  Endothelium-dependent vasodilatation is not affected by blocking prostaglandin release or KATP channels in the intact heart even in the presence of an anaesthetic. However, the diminished responses to vasodilators after nitric oxide synthase inhibition is largely restored or enhanced by anaesthetics.
authors.affiliation: Anesthesiology Research Laboratory, Department of Anesthesiology and the Cardiovascular Research Center, Medical College of Wisconsin, and Research Service, VA Medical Center, Milwaukee, WI 53226 USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Stowe
authors.forename: J S
authors.initials: JS
authors.lastname: Heisner
authors.forename: W W
authors.initials: WW
authors.lastname: Chung
authors.forename: S
authors.initials: S
authors.lastname: Fujita
mesh_terms: D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D054086:KATP Channels; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011448:Prostaglandin Antagonists; C092520:uK-ATP-1 potassium channel; D012701:Serotonin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin