Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats.
OBJECTIVE
We tested the hypothesis that inhibition of nitric oxide synthase activity in brain before ischemia alters cerebral blood flow and decreases brain injury after 4 hours of middle cerebral artery occlusion in cats.


METHODS
Halothane-anesthetized cats underwent 4 hours of left middle cerebral artery occlusion after they were randomly assigned to receive either intravenous N omega-nitro-L-arginine methyl ester, at a dose that completely inhibited cortical nitric oxide synthase activity (10 mg/kg, n = 10), or an equal volume of diluent (10 mL saline, n = 10). Serial blood flow measurements were made with radiolabeled microspheres, and injury volume was measured by triphenyltetrazolium staining.


RESULTS
Blood flow to caudate nucleus and inferior temporal cortex decreased to the same extent in both groups during middle cerebral artery occlusion. Somatosensory evoked potential amplitude was reduced to less than 10% of baseline values in both groups. Injury volume of ipsilateral caudate nucleus in cats pretreated with nitroarginine (52 +/- 5%, mean +/- SE) was less (P < .05) compared with the saline group (80 +/- 4%), whereas ipsilateral cerebral hemispheric injury volume was similar between the two groups (30 +/- 6% and 32 +/- 4% of hemisphere in saline and nitroarginine groups, respectively).


CONCLUSIONS
These results suggest that inhibition of nitric oxide synthase decreases caudate injury volume at 4 hours of middle cerebral artery occlusion without an alteration in distribution of cerebral blood flow.
Nishikawa
T
T
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Md.
Kirsch
J R
JR
Koehler
R C
RC
Bredt
D S
DS
Snyder
S H
SH
Traystman
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D002415:Cats; D002421:Caudate Nucleus / Q000098:blood supply; D002531:Cerebellum / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000098:blood supply; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010296:Parietal Lobe / Q000098:blood supply; D012039:Regional Blood Flow / Q000187:drug effects; D013702:Temporal Lobe / Q000098:blood supply
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester