Evidence for a K-ATP ion channel link in the inhibition of hypercapnic dilation of pial arterioles by 7-nitroindazole and tetrodotoxin

7-Nitroindazole, an inhibitor of neuronal nitric oxide synthase, reportedly inhibits hypercapnic dilation, but tetrodotoxin, an inhibitor of neuronal transmission, reportedly does not. Thus, evidence does not uniformly suppor t the hypothesis of a neurogenic Link to the hypercapnic response. Others s uggest the hypercapnic response is mediated by a K-ATP ion channel. In the following studies, we observed that topically administered tetrodotoxin inh ibited dilations produced by hypercapnia. In addition, topical tetrodotoxin and either topical or intraperitoneal 7-nitroindazole, inhibited dilations produced by the K-ATP channel openers, cromakalim and pinacidil. Inhibitio n of hypercapnic dilation and inhibition of dilation by the openers of the K-ATP channel was immediately reversed by either L-lysine or (L)-arginine, amino acids previously shown to facilitate opening of the channel. The data strongly supports the previous conclusion that there is a K-ATP ion channe l Link in the response of pial arterioles to hypercapnia. The location of t he channel is not established by these data, nor is it known whether the ac tion of tetrodotoxin on the channel was direct or indirect. (C) 2001 Publis hed by Elsevier Science B.V.