Inhibition of nitric oxide synthesis: effects on cerebral blood flow and glucose utilisation in the rat.
The consequences of inhibition of nitric oxide synthesis on local CBF and glucose utilisation have been studied in the conscious rat using the specific nitric oxide synthase inhibitor Ng-nitro-L-arginine methyl ester (L-NAME; 30 mg kg-1 i.v.). Local CBF and glucose utilisation were assessed with the [14C]iodoantipyrine and the 2-deoxy-D-[14C]glucose autoradiographic techniques, respectively. L-NAME induced prolonged (> 3 h) reductions in local CBF throughout the CNS with concomitant increases in arterial blood pressure. For example, 1 h post L-NAME, CBF dropped from 79 +/- 4 to 45 +/- 1 ml 100 g-1 min-1 in cerebellum, from 76 +/- 4 to 47 +/- 2 ml 100 g-1 min-1 in medulla oblongata, and from 117 +/- 6 to 72 +/- 2 ml 100 g-1 min-1 in cortex. L-NAME produced sustained elevations (e.g., 46 +/- 2 mm Hg at 1 h after bolus administration) in mean arterial blood pressure throughout the period evaluated. Despite evidence implicating nitric oxide in neuronal signalling, L-NAME did not significantly influence CNS functional activity, as measured by local rates of glucose utilisation, in any neuroanatomical region examined. Consequently, the normal ratio of blood flow to glucose use throughout the brain was significantly reduced in the presence of L-NAME, although the hierarchy of blood flow levels in different neuroanatomical regions was preserved. These results are consistent with the involvement of nitric oxide in the tonic control of cerebral tissue perfusion.
Macrae
I M
IM
Wellcome Neuroscience Group, Wellcome Surgical Institute, Glasgow, Scotland.
Dawson
D A
DA
Norrie
J D
JD
McCulloch
J
J
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D001120:Arginine; D003847:Deoxyglucose; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D005947:Glucose; D000983:Antipyrine; C008135:iodoantipyrine; D019331:NG-Nitroarginine Methyl Ester