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

AbstractTo determine whether endogenous nitric oxide (NO) opens the ATP-sensitive K+ channel (KATP 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 KATP channel. Activation of this channel was suppressed by pretreatment with 10−3 M NG-methyl-l-arginine or 10−3 M Nx-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 KATP channel by l-arginine-NO pathway is expected to produce hyperpolarization of the cell membrane and relaxation of vascular smooth muscle cells