title: Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow.
abstract: We tested the hypothesis that NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/- 4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE) ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10 micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x 100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L-NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O2 transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287.
authors.forename: R W
authors.initials: RW
authors.lastname: McPherson
authors.forename: R C
authors.initials: RC
authors.lastname: Koehler
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; 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 / Q000502:physiology*; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D020926:Medetomidine; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009928:Organ Specificity; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010313:Partial Pressure; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D002245:Carbon Dioxide; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D020926:Medetomidine; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester