Nitric oxide synthase inhibition attenuates hypoglycemic cerebral hyperemia in piglets.
We tested the hypothesis that nitric oxide (NO) mediates hypoglycemia-induced cerebral vasodilation in piglets. Piglets (1-2 wk old) were made hypoglycemic with insulin (200 U/kg i.v.) with and without an NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg i.v.). Electroencephalogram (EEG), cerebral O2 consumption (CMRO2), and cerebral blood flow (CBF) were measured before L-NAME and insulin and for 180 min after insulin. Hypoglycemia led to isoelectric EEG earlier after L-NAME (87 +/- 8 min) than without L-NAME pretreatment (132 +/- 13 min). CBF increased in all brain regions during hypoglycemia at the onset of isoelectric EEG and was associated with increased CMRO2.L-NAME prevented the increase in CMRO2 and attenuated vasodilation in forebrain (154 +/- 37 vs. 400 +/- 60%), cerebellum (251 +/- 52 vs. 386 +/- 52%), and cortical gray matter (183 +/- 47 vs. 524 +/- 93%) but had no effect on CBF responses in brain stem, thalamus, caudate, or hippocampus. We conclude that NO or a NO-containing compound mediates cerebral vasodilation induced by profound insulin-hypoglycemia in piglets and that this vasodilation plays an important role in the adaptation of immature brain to hypoglycemia.
Ichord
R N
RN
Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287.
Helfaer
M A
MA
Kirsch
J R
JR
Wilson
D
D
Traystman
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004569:Electroencephalography; D005990:Glycerol; D006940:Hyperemia / Q000503:physiopathology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D013552:Swine
D007328:Insulin; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D005990:Glycerol; D019331:NG-Nitroarginine Methyl Ester