title: Cardiac and regional hemodynamic interactions between halothane and nitric oxide synthase activity in dogs.
abstract: BACKGROUND
  In vitro, halothane appears to affect the role played by nitric oxide in the regulation of vascular tone and cardiac function. In vivo, the results of the interactions between halothane and the nitric oxide pathway remain controversial. The authors investigated the effects of halothane on the cardiac and regional hemodynamic properties of N-methyl-L-arginine (NMA), a specific nitric oxide synthase inhibitor, in dogs.
  
  
  METHODS
  Twenty-five dogs were chronically instrumented. Aortic pressure, the first derivative of left ventricular pressure, cardiac output, heart rate, and carotid, coronary, mesenteric, hepatic, portal and renal blood flows were continuously recorded. N-methyl-L-arginine was infused intravenously at 20 mg/kg over 1 min in awake dogs (n = 11) and in 1.2% halothane-anesthetized dogs (n = 10). As a control group, the remaining four dogs were studied awake and during 1.2% halothane for 2 h in the absence of NMA.
  
  
  RESULTS
  In awake dogs, NMA produced a sustained pressor response (34%) and systemic vasoconstriction (40%) associated with a decrease in cardiac output (16%). Regional circulation changes included an immediate and transient increase in carotid (43%) and coronary (237%) blood flows and a subsequent decrease in carotid blood flow (25%). Hepatic and mesenteric blood flows also decreased, by 43% and 16%, respectively. Except for the coronary circulation, regional vascular resistance increased significantly. Halothane did not affect the pressor response to NMA but did blunt the cardiac output changes. Consequently, the systemic vasoconstriction after nitric oxide synthase inhibition was of shorter duration and of lesser magnitude during halothane anesthesia. Halothane also blunted the carotid, mesenteric, and renal vasoconstriction induced by NMA. Finally, in 1.2% halothane-anesthetized dogs, NMA induced a coronary vasoconstriction.
  
  
  CONCLUSIONS
  Halothane minimally interferes with the systemic and regional hemodynamic consequences of nitric oxide synthase blockade. The nature and magnitude of the interaction depend on the territory in which they occur.
authors.affiliation: Department of Anesthesiology, University of Texas Health Science Center, Medical School at Houston 77030, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Chelly
authors.forename: M F
authors.initials: MF
authors.lastname: Doursout
authors.forename: T
authors.initials: T
authors.lastname: Lechevalier
authors.forename: Y Y
authors.initials: YY
authors.lastname: Liang
authors.forename: F
authors.initials: F
authors.lastname: Chelly
authors.forename: C
authors.initials: C
authors.lastname: Hartley
authors.forename: R G
authors.initials: RG
authors.lastname: Kilbourn
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019323:omega-N-Methylarginine
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D006221:Halothane