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 (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.