title: Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs.
abstract: BACKGROUND
  The mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine.
  
  
  METHODS
  The cerebral blood flow (microsphere) response to 1 MAC isoflurane was tested at three time points (0, 90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologic intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isoflurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isoflurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isoflurane challenge (n = 8).
  
  
  RESULTS
  In control animals, isoflurane reproducibly increased cerebral blood flow (whole brain; 113 +/- 18%, 120 +/- 18%, and 103 +/- 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 +/- 10% and 52 +/- 11% increase, respectively) the hyperemic response to isoflurane. The effect of L-NAME was reversed by L-arginine.
  
  
  CONCLUSIONS
  We conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: L E
authors.initials: LE
authors.lastname: Moore
authors.forename: J R
authors.initials: JR
authors.lastname: Kirsch
authors.forename: M A
authors.initials: MA
authors.lastname: Helfaer
authors.forename: J R
authors.initials: JR
authors.lastname: Tobin
authors.forename: R W
authors.initials: RW
authors.lastname: McPherson
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D006940:Hyperemia / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology*; D007530:Isoflurane / Q000009:adverse effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000097:blood; D013552:Swine
chemical_list: D002245:Carbon Dioxide; D009569:Nitric Oxide; D001120:Arginine; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin