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Am J Physiol Heart Circ Physiol 274: H974-H981, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 3, H974-H981, March 1998

Cerebral arteriolar dilations by KATP channel activators need L-lysine or L-arginine

Hermes A. Kontos and Enoch P. Wei

Department of Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298

We investigated the effects of various amino acids on responses to ATP-sensitive potassium (KATP) channel openers in anesthetized cats equipped with cranial windows. The application of pinacidil by superfusion caused transient vasodilation, whereas there was sustained vasodilation from the application of stationary solution of pinacidil. In the presence of L-arginine or L-lysine, pinacidil by superfusion led to sustained vasodilation, suggesting that the rapid flow of fluid displaced these amino acids from binding on the channel and that such binding was essential for opening the channel. NG-nitro-L-arginine blocked responses to pinacidil, and this blockade was reversed by L-lysine or L-arginine but not by D-arginine, D-lysine, methyl-L-arginine, glycine, L-histidine, dimethylarginine, dimethyl-L-arginine, or hydroxylysine. The blockade of responses to pinacidil induced by glyburide was also reversed completely by L-arginine or L-lysine but not by D-arginine, suggesting that these amino acids act on the sulfonylurea receptor. Hydroxylysine but not methyl-L-lysine, dimethylarginine, or dimethyl-L-arginine blocked responses to pinacidil. The findings show that KATP channels in cerebral arterioles need L-lysine or L-arginine to open in response to agonists.

vasodilation; cerebral circulation; vascular smooth muscle; membrane ion channels; glyburide


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