Inhibition of nitric oxide synthase does not affect alpha 2-adrenergic-mediated cerebral vasoconstriction.
We assessed whether blocking nitric oxide (NO) synthase alters the cerebral blood flow (CBF) response to alpha 2-adrenergic stimulation during isoflurane anesthesia in dogs. In control animals (n = 6), CBF (microspheres), cerebral oxygen consumption (CMRO2), and electroencephalograph (EEG) were measured after 1 h of isoflurane (1.4% end-tidal) and before and 5, 10, and 20 min after injection of an alpha 2-adrenergic receptor agonist (dexmedetomidine 10 micrograms/kg, intravenous bolus). Dogs in a second group (n = 6) were treated similar to control animals except that an irreversible blocker of NO synthase, N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg) was administered 1 h before induction of anesthesia. In control dogs, dexmedetomidine decreased CBF by 37% (P < 0.05). Blood flow remained decreased for the 20 min observation period in all brain regions except cerebellum and caudate. In the L-NAME group, control CBF was 45% less than baseline flow in the control group (P < 0.05) and dexmedetomidine further decreased CBF from 41 +/- 7 mL x 100 g-1 x min-1 to 24 +/- 2 mL.100 g-1 x min-1 (P < 0.05). There was no difference between groups in the percent of reduction of blood flow in any region after dexmedetomidine administration. Control CMRO2 was similar in the two groups and was unchanged by dexmedetomidine. These data demonstrate that L-NAME reduces CBF and that block of NO synthase does not affect alpha 2-adrenergic-mediated decreases in CBF during isoflurane anesthesia.
McPherson
R W
RW
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Kirsch
J R
JR
Traystman
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D020926:Medetomidine; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D002245:Carbon Dioxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D020926:Medetomidine; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester