抄録
The present study was designed to examine the role of basally released nitric oxide in relaxations to an ATP-sensitive K+ channel opener. Whether relaxations to levcromakalim are modulated by endothelial removal or the inhibitors of vasodilator effects of endothelium-derived nitric oxide, were investigated in the rat aorta. During contractions to phenylephrine (3×10-7 to 10-6 M), levcromakalim (10-8 to 10-5 M) or a nitric oxide donor, 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7, 10-9 to 10-5 M), was added in a cumulative fashion. Relaxations to levcromakalim (10-8 to 10-5 M) were significantly reduced by the endothelium-removal. In aortas with endothelium, relaxations in response to levcromakalim were decreased by selective inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester, 10-4 M) and soluble guanylate cyclase (1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxaline-1-one; ODQ, 10-5 M) and a scavenger of nitric oxide (carboxy-PTIO, 10-3 M). Relaxations to levcromakalim in aortas treated with these inhibitors are comparable to those seen in aortas without endothelium. KCl (30 mM) and an ATP-sensitive K+ channel inhibitor, glibenclamide (10-5 M), abolished relaxations to levcromakalim in aortas with or without endothelium, whereas glibenclamide did not alter relaxations to NOC-7 (10-9 to 10-5 M) in aortas without endothelium. These results suggest that in rat aortas, inhibition of vasodilator effects of basally released nitric oxide can reduce relaxations via ATP-sensitive K+ channels, although these channels do not mediate relaxations to exogenously applied nitric oxide.
