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 neurotransmitter, is vasoactive in the cerebral circulation. However, the mechanism is unclear. This study was designed to investigate the role of nitric oxide (NO) and N-methyl-D-aspartate (NMDA) receptors in cerebral arteriolar dilation to glutamate. Methods Newborn, chloralose-anesthetized pigs were equipped with a closed cranial window. The diameter of pial arterioles was measured by means of intravital microscopy, and NO synthase (NOS) activity in brain cortex was determined by the conversion assay of [C-14]arginine to [C-14]citrulline. Results Topical application 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), respectively (baseline, 91+/-10 mu m; P<.05). Similarly, NMDA application at the 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 activity by 93%, blocked the arteriolar dilation to glutamate or NMDA. Furthermore, administration of MK-801, a potent inhibitor of NMDA receptors, blocked glutamate-induced vasodilation completely in both topical application (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 vasodilation to hypercapnia (PCO2=40 to 68 mm Hg). Conclusions Glutamate-induced cerebral arteriolar dilation is mediated by NO through NMDA receptors, and NO does not play a major role in the cerebral arteriolar dilation to hypercapnia (P-CO2=40 to 68 mm Hg) in newborn pigs.