The vasodilating mechanism of a new compound, cyanoimino-3-pyridylmethylaminoethyl nitrate methanesulfonate (KRN2391), a derivative of nicorandil, was examined in the isolated rabbit aorta. To elucidate the structure activity relationship, a comparison was made with the two denitrated derivatives: cyanoimino-3-pyridylmethylaminoethyl acetate methanesulfonate (Ki4032) and cyanoimino-3-pyridylmethylaminoethyl alcohol (Ki3315). In preparations precontracted with phenylephrine (10(-7) mol/l), KRN2391, Ki4032 and Ki3315 caused concentration-dependent relaxation. pD2 values (-log [EC50]) were 6.74 +/- 0.03, 5.67 +/- 0.05 and 3.63 +/- 0.03, respectively. Both methylene blue and glibenclamide produced a shift to the right of the concentration-response curves for KRN2391. The shift by glibenclamide became greater in the presence of methylene blue. An elevation of the cGMP content was not detected until the concentration of KRN2391 was increased to a level enough to produce a full relaxation (3 x 10(-6) mol/l). In contrast, in the case of Ki3315 a parallel shift to the right of the concentration-response curve was observed after glibenclamide (10(-5) mol/l). Methylene blue (10(-5) mol/l) had no effect on the concentration-response curve, and there was no increase in cyclic GMP (cGMP) with 10(-3) mol/l of the compound. The concentration-response curve of Ki4032 was also attenuated by glibenclamide. Though this compound lacks the nitrate moiety, it (10(-4) mol/l) showed a slight tendency to increase the cGMP content, and methylene blue slightly but significantly modified the concentration-response curve of this compound. However, the co-administration of glibenclamide and methylene blue resulted in no further modification of the concentration-relaxation curve.(ABSTRACT TRUNCATED AT 250 WORDS)