Vasodilator effects of sodium nitroprusside, levcromakalim and their combination in isolated rat aorta

1 The endothelial modulation of the relaxant responses to the nitric oxide (NO) donor sodium nitroprusside (SNP) and the K-ATP channel opener levcroma kalim (LEM) and the interactions between these agents were analysed in isol ated rat aorta. 2 LEM-induced relaxation was unchanged by endothelium removal or by the pre sence of L-NAME (10(-4) M) or ODQ (10(-6) M). In contrast, in KCl- (25 mM), but not in noradrenaline- (NA, 10(-6) M) contracted arteries, SNP-induced relaxation was augmented by endothelium removal but not by L-NAME, indometh acin, glibenclamide nor charybdotoxin plus apamin. 3 The isobolographic analysis of the interactions between exogenously activ ated KATP channels and cyclic GMP using mixtures of SNP and LEM revealed th at there were no interactions between both drugs at the proportions at whic h both drugs were active. However, the points for the SNP:LEM mixtures in p roportions 10:1 and 1:10,000 (i.e. at concentrations at which LEM and SNP w ere inactive, respectively) fell significantly above the line of additivity indicating that there were negative interactions between both drugs at the se selected proportions (about 5- and 2 fold inhibition, respectively). The former interaction was sensitive to glibenclamide, whereas the latter was insensitive ODQ. The magnitude of the 10:1 SNP:LEM interaction was smaller in endothelium-intact arteries and was absent in arteries stimulated by NA. 4 In conclusion, the relaxations induced by LEM and SNP were additive. Howe ver, the presence of endothelium and low concentrations of LEM inhibited SN P-induced relaxation. Both inhibitory effects were not additive and were on ly observed in KCl- and not in NA-contracted aortae.