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 support the hypothesis of a neurogenic link to the hypercapnic response. Others suggest the hypercapnic response is mediated by a K_ATP ion channel. In the following studies, we observed that topically administered tetrodotoxin inhibited 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. Inhibition 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 channel link in the response of pial arterioles to hypercapnia. The location of the channel is not established by these data, nor is it known whether the action of tetrodotoxin on the channel was direct or indirect.