Dilatation of cerebral arterioles in response to N-methyl- d-aspartate : role of CGRP and acetylcholine

Abstract

The purpose of these experiments was to examine mechanisms by which N-methyl- d-aspartate (NMDA) produces nitric oxide-dependent vasodilatation in brain. Some nitrovasodilators appear to dilate cerebral arterioles, in part, by release of calcitonin gene-related peptide (CGRP) from trigeminal fibers. The first goal of this study was to examine the hypothesis that dilatation of cerebral arterioles in response to NMDA is mediated by activation of receptors for CGRP. Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Topical CGRP (1 and 10 nM) dilated cerebral arterioles by 30 ± 9 (mean±S.E.M.) and 72 ± 9%, respectively, from a control diameter of 94 ± 7 μm. This response was inhibited almost completely by the CGRP antagonist CGRP(8–37) (0.5 μM). NMDA (100 and 300 μM) dilated cerebral arterioles by 14 ± 5and38 ± 7% in the absence and 20 ± 5%and30 ± 6% in the presence, respectively, of CGRP(8–37). Neurons may release acetylcholine in response to activation with NMDA. The second goal of the present study was to examine the hypothesis that dilatation of cerebral arterioles in response to NMDA is mediated by acetylcholine. Topical atropine (2 μg/ml) completely inhibited dilatation of cerebral arterioles in response to acetylcholine, but had no effect on vasodilatation in response to NMDA. Thus, vasodilatation of cerebral arterioles in response to NMDA does not appear to be dependent on activation of receptors for CGRP or acetylcholine.