GLUTAMATE-INDUCED CEREBRAL VASODILATION IS MEDIATED BY NITRIC-OXIDE THROUGH N-METHYL-D-ASPARTATE RECEPTORS

Background and Purpose It was found that glutamate, a major neurotrans mitter, is vasoactive in the cerebral circulation. However, the mechan ism is unclear. This study was designed to investigate the role of nit ric oxide (NO) and N-methyl-D-aspartate (NMDA) receptors in cerebral a rteriolar dilation to glutamate.Methods Newborn, chloralose-anesthetiz ed pigs were equipped with a closed cranial window. The diameter of pi al arterioles was measured by means of intravital microscopy, and NO s ynthase (NOS) activity in brain cortex was determined by the conversio n assay of [C-14]arginine to [C-14]citrulline. Results Topical applica tion of glutamate at 10(-7), 10(-6), and 10(-5) mol/L (n=5) increased the mean diameter by 12+/-3%, 13+/-2%, and 18+/-3% (+/-SEM), respectiv ely (baseline, 91+/-10 mu m; P<.05). Similarly, NMDA application at th e above doses (n=5) dilated arterioles by 10+/-2% 16+/-3%, and 18+/-6% , respectively (baseline, 97+/-4 mu m; P<.05). Topical application of 10(-4) mol/L N-G-nitro-L-arginine (L-NNA), which inhibited NOS activit y by 93%, blocked the arteriolar dilation to glutamate or NMDA. Furthe rmore, administration of MK-801, a potent inhibitor of NMDA receptors, blocked glutamate-induced vasodilation completely in both topical app lication (10(-5) mol/L n=6) and intravenous administration (5 to 10 mg /kg; n=5). In addition, neither L-NNA nor MK-801 attenuated the vasodi lation to hypercapnia (PCO2=40 to 68 mm Hg). Conclusions Glutamate-ind uced cerebral arteriolar dilation is mediated by NO through NMDA recep tors, and NO does not play a major role in the cerebral arteriolar dil ation to hypercapnia (P-CO2=40 to 68 mm Hg) in newborn pigs.