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

To 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.