Responses of cerebral arterioles to kainate.
OBJECTIVE
Neurons release nitric oxide in response to glutamate. Glutamate acts via activation of different receptor subtypes, including N-methyl-D-aspartate and kainate receptors. This study examined the hypothesis that kainate produces dilatation of cerebral arterioles that is dependent on the formation of nitric oxide.


METHODS
Diameters of cerebral arterioles were measured by means of a closed cranial window in anesthetized rabbits. Kainate, quisqualate, acetylcholine, and NG-nitro-L-arginine (L-NNA, an inhibitor of nitric oxide synthase) were applied locally in the cranial window. We also examined whether kainate elicited direct vascular effects by the use of isolated cerebral arteries in vitro.


RESULTS
Under control conditions, topical kainate (100 mumol/L) increased the diameter of arterioles by 20 +/- 5% (mean +/- SE), 27 +/- 7%, and 31 +/- 7% at 3, 5, and 9 minutes of application, respectively. After topical application of L-NNA (300 mumol/L), kainate dilated cerebral arterioles by 8 +/- 4%, 9 +/- 5%, and 8 +/- 6% at 3, 5, and 9 minutes, respectively (P < .05 versus the control response). In contrast, quisqualate (100 and 300 mumol/L) did not alter the diameter of cerebral arterioles. In rings of the middle cerebral artery studied in vitro, kainate had no effect on vascular tone, which suggests that cerebral vessels lack receptors for kainate. Thus, cerebral vasodilator effects of kainate do not appear to be due to the direct effect of the excitatory amino acid on cerebral vessels.


CONCLUSIONS
These findings suggest that kainate produces dilatation of cerebral arterioles in vivo that is mediated by release of nitric oxide from an extravascular source.
Faraci
F M
FM
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Breese
K R
KR
Heistad
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D006632:Histamine / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000493:pharmacokinetics; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D006632:Histamine; D016318:Quisqualic Acid; D001120:Arginine; D000109:Acetylcholine; D007608:Kainic Acid