EXAMINATION OF POTENTIAL MECHANISMS IN THE ENHANCEMENT OF CEREBRAL BLOOD-FLOW BY HYPOGLYCEMIA AND PHARMACOLOGICAL DOSES OF DEOXYGLUCOSE

Cerebral blood flow (CBF) rises when the glucose supply to the brain i s limited by hypoglycemia or glucose metabolism is inhibited by pharma cological doses of 2-deoxyglucose (DG). The present studies in unanest hetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [C-14]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was e xcluded; insulin administered under euglycemic conditions maintained b y glucose injections had no effects on CBF. Insulin administration rai sed plasma lactate levels and decreased plasma K+ and HCO3- concentrat ions and arterial pH. These could not, however, be related to the incr eased CBF because insulin under euglycemic conditions had similar effe cts without affecting CBF; furthermore, the inhibition of brain glucos e metabolism with pharmacological doses (200 mg/kg intravenously) of D G increased CBF, just like insulin hypoglycemia, without altering plas ma lactate and K+ levels and arterial blood gas tensions and pH. Nitri c oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p, injecti ons of NG-nitro-L-arginine methyl ester for 4 days or acutely by a sin gle i.v. injection raised arterial blood pressure and lowered CBF in n ormoglycemic, hypoglycemic, and DG-treated rats but did not significan tly reduce the increases in CBF due to insulin-induced hypoglycemia (a rterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of d eoxyglucose.