NONENDOTHELIAL-DERIVED NITRIC-OXIDE ACTIVATES THE K+ CHANNELS IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

Endotoxin induces an enzyme that synthesizes nitric oxide (NO) from L-arginine in vascular smooth muscle cells, resulting in nonendothelial NO release. We measured the NO release and its intracellular action on the Ca2+-activated K+ channel (K-Ca channel) and the ATP-sensitive K+ channel (K-ATP channel) in cultured smooth muscle cells of porcine coronary artery using an NO sensor and a patch-clamp technique. In endotoxin-pretreated cells, L-arginine-100 mu M increased NO release, which activated both the K-Ca and K-ATP channels. These effects were suppressed by pretreatment with 1 mM N-omega-nitro-L-arginine methyl ester, an antagonist of the L-arginine-NO pathway. Methylene blue 1 mu M, a blocker of guanylate cyclase, inhibited L-arginine-induced activation of these channels, suggesting modulation by cGMP. Our results suggest that the nonendothelial-derived NO modulates both K-Ca and K-ATP channels and that it controls vascular tone by opening the K+ channels. The activation of the K+ channels may be an important factor for sustained vasodilation in endotoxin shock.