(Stroke. 1995;26:857-863.)
© 1995 American Heart Association, Inc.
Articles |
Glutamate-Induced Cerebral Vasodilation Is Mediated by Nitric Oxide Through N-Methyl-D-Aspartate Receptors
From the Departments of Physiology and Pharmacology (W.M.), Anesthesiology (J.R.T.), and the Neuroscience Program (D.W.B.), Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC.
Correspondence to David W. Busija, PhD, Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1083.
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 [14C]arginine to [14C]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 µm; 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 µm; P<.05). Topical application of 10-4 mol/L NG-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 (PCO2=40 to 68 mm Hg) in newborn pigs.
Key Words: pigs • cerebral circulation • nitric oxide • glutamate • N-methyl-D-aspartate
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