Role of Na+/H+ exchanger in dilator responses of rat basilar artery in vivo

We tested the hypothesis that activation of Na+/H+ exchanger is involved in dilator responses of the basilar artery to endothelium-dependent vasodilat ors in vivo. Using a cranial window in anesthetized rats. we examined respo nses of the basilar artery to acetylcholine and bradykinin. Topical applica tion of acetylcholine and bradykinin increased diameter of the basilar arte ry in a concentration-related manner. Because N-G-nitro-L-arginine, an inhi bitor of nitric oxide synthase, almost abolished vasodilator responses to a cetylcholine and bradykinin, vasodilatation produced by the agonists appear s to be mediated primarily by nitric oxide. 5-N,N-Hexamethyleneamiloride, a n inhibitor of Na+/H+ exchanger, did not affect baseline diameter of the ba silar artery, but inhibited vasodilatation in response to acetylcholine and bradykinin, without affecting vasodilatation produced by sodium nitropruss ide. FR 183998, another inhibitor of Na+/H+ exchanger, also attenuated acet ylcholine-induced dilatation of the basilar artery without affecting vasodi latation in response to sodium nitroprusside. Monomethylamine hydrochloride , which produces intracellular alkalinization, enhanced acetylcholine-induc ed dilatation of the basilar artery in the presence of 5-N,N-hexamethylenea miloride. These results suggest that intracellular alkalinization produced by activation of Na+/H+ exchanger may enhance nitric oxide production in th e basilar arterial endothelium and thereby contribute to dilator responses of the artery in vivo. (C) 2001 Elsevier Science B.V. All rights reserved.