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 ma de hypoglycemic with insulin (200 U/kg iv) with and without an NO synt hase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/k g iv). Electroencephalogram (EEG), cerebral O-2 consumption (CMR(O2)), and cerebral blood flow (CBF) were measured before L-NAME and insulin and for 180 min after insulin. Hypoglycemia led to isoelectric EEG ea rlier after L-NAME (87 +/- 8 min) than without L-NAME pretreatment (13 2 +/- 13 min). CBF increased in all brain regions during hypoglycemia at the onset of isoelectric EEG nd was associated with increased CMR(O 2). L-NAME prevented the increase in CMR(O2) and attenuated vasodilati on in forebrain (154 +/- 37 vs. 400 +/- 60%), cerebellum (251 +/- 52 v s. 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 mediat es cerebral vasodilation induced by profound insulin-hypoglycemia in p iglets and that this vasodilation plays an important role in the adapt ation of immature brain to hypoglycemia.