Nonendothelial‐derived nitric oxide activates the ATP‐sensitive K+ channel of vascular smooth muscle cells

Abstract

To determine whether endogenous nitric oxide (NO) opens the ATP-sensitive K⁺ channel (K_ATP channel), we investigated the effect of nonendothelial-derived NO on this channel in cultured smooth muscle cells of the porcine coronary artery by the patch-clamp technique. In the cells pretreated with endotoxin, the addition of 10⁻⁴ M l-arginine generated NO and activated the K_ATP channel. Activation of this channel was suppressed by pretreatment with 10⁻³ M N ^G-methyl-l-arginine or 10⁻³ M N ^x-nitro-l-arginine methyl ester, each of which is a specific antagonist of the l-arginine-NO pathway, and by 10⁻⁶ M Methylene blue, which blocks guanylate cyclase. The activation of the K_ATP channel by l-arginine-NO pathway is expected to produce hyperpolarization of the cell membrane and relaxation of vascular smooth muscle cells.