CEREBRAL ARTERIOLAR DILATIONS BY K-ATP CHANNEL ACTIVATORS NEED L-LYSINE OR L-ARGININE

We investigated the effects of various amino acids on responses to ATP -sensitive potassium (K-ATP) channel openers in anesthetized cats equi pped with cranial windows. The application of pinacidil by superfusion caused transient vasodilation, whereas there was sustained vasodilati on from the application of stationary solution of pinacidil. In the pr esence of L-arginine or L-lysine, pinacidil by superfusion led to sust ained vasodilation, suggesting that the rapid flow of fluid displaced these amino acids from binding on the channel and that such binding wa s essential for opening the channel. N-G-nitro-L-arginine blocked resp onses to pinacidil, and this blockade was reversed by L-lysine or L-ar ginine but not by D-arginine, D-lysine, methyl-L-arginine, glycine, L- histidine. dimethylarginine, dimethyl-L-arginine, or hydroxylysine. Th e blockade of responses to pinacidil induced by glyburide was also rev ersed completely by L-arginine or L-lysine but not by D-arginine, sugg esting that these amino acids act on the sulfonylurea receptor. Hydrox ylysine but not methyl-L-lysine, dimethylarginine, or dimethyl-L-argin ine blocked responses to pinacidil. The findings show that K-ATP chann els in cerebral arterioles need L-lysine or L-arginine to open in resp onse to agonists.