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Stroke. 1995 May;26(5):857-62; discussion 863.

Glutamate-induced cerebral vasodilation is mediated by nitric oxide through N-methyl-D-aspartate receptors.

Author information

1
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA.

Abstract

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 microns; 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 microns; 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.

PMID:
7740580
DOI:
10.1161/01.str.26.5.857
[Indexed for MEDLINE]

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