title: L-arginine and nitroglycerin restore hypercapnia-induced cerebral vasodilation in rabbits after its attenuation by ketamine.
abstract: Although it has been reported that ketamine attenuates hypercapnia-induced cerebral vasodilation, the mechanism remains unknown. Because nitric oxide is involved in cerebral CO2 reactivity, we studied the effects of L-arginine and nitroglycerin on ketamine-mediated attenuation of vascular responses to hypercapnia. Under pentobarbital anesthesia, 16 rabbits underwent closed cranial window preparation. Hypercapnic challenges were repeated after IV saline, ketamine (10 mg/kg, followed by 20 mg x kg(-1) x h(-1)), or ketamine plus either L-arginine (150 mg/kg, followed by 100 mg x kg(-1) x h(-1); n = 8) or nitroglycerin (5 microg x kg(-1) x min(-1) infusion; n = 8). Ketamine reduced hypercapnia-induced cerebral vasodilation (1.27%/mm Hg +/- 0.45%/mm Hg [saline] versus 0.82%/mm Hg +/- 0.53%/mm Hg [ketamine]: P < 0.05), but L-arginine restored reactivity (1.28%/mm Hg +/- 0.73%/mm Hg: P < 0.05 versus ketamine), as did nitroglycerin (1.14%/mm Hg +/- 0.73%/mm Hg [saline] versus 0.56%/mm Hg +/- 0.63%/mm Hg [ketamine]: P < 0.05, and 1.15%/mm Hg +/- 0.74%/mm Hg [ketamine plus nitroglycerin]: P < 0.05 versus ketamine). This indicates that ketamine attenuates cerebral CO2 reactivity, at least in part, via suppression of nitric oxide-cyclic guanosine monophosphate mechanisms in the cerebral vasculature.
  
  
  CONCLUSIONS
  The attenuation of cerebral vasodilation to hypercapnia seen under ketamine anesthesia is reversed by L-arginine or nitroglycerin infusion.
authors.affiliation: Department of Anesthesiology & Critical Care Medicine, Gifu University School of Medicine, Gifu City, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nagase
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.forename: Shuji
authors.initials: S
authors.lastname: Dohi
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology*; D007649:Ketamine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D009569:Nitric Oxide; D007649:Ketamine; D001120:Arginine; D005996:Nitroglycerin