Effects of nicorandil as compared to mixtures of sodium nitroprusside and levcromakalim in isolated rat aorta

1 The contribution of the relaxant mechanisms of nicorandil (NIC) were anal ysed by comparing its effects with those of sodium nitroprusside (SNP), lev cromakalim (LEM) and mixtures (1:10, 1:30 and 1:100) of SNP:LEM in isolated endothelium-denuded rat aorta. 2 In rings precontracted with KCI (25 mM), the relative inhibitory potency of the soluble guanylate cyclase inhibitor ODQ and the K-ATP channel inhibi tor glibenclamide (GLI) on SNP:LEM mixtures showed a good correlation with the relative proportion of SNP and LEM in the mixtures. Furthermore, the de gree of the inhibition by ODQ and GLI of the effects of the 1:30 SNP:LEM mi xture varied as a function of the relative potency of SNP and LEM in KCl-, noradrenaline- (NA) or NA plus nifedipine-treated arteries. 3 The inhibitory effects of ODQ, GLI and ODQ plus GLI on NIC-induced relaxa tion was similar to that for the 1:30 SNP:LEM mixture in NA plus nifedipine -contracted arteries, but the inhibition of GLI or ODQ plus GLI was smaller in KCI-contracted arteries. 4 In conclusion, the relative importance of activation of the cyclic GMP pa thway and KATP channel opening in mixtures of SNP and LEM could be predicte d by the proportion of the drugs in the mixtures and by the relative potenc y of SNP vs LEM in different experimental conditions. Furthermore, the pres ent results suggest that besides these two mechanisms, a third ODQ- and GLI -insensitive mechanism, possibly involving Ca2+ channel blockade, also part icipates in the relaxant effects of NIC in KCl-induced contractions.