Mechanisms of inhibitory effects of CD-349 and K(+)-channel activators on noradrenaline-induced contraction and changes in levels of cyclic GMP in rat aorta.

1. CD-349 inhibited the noradrenaline (NA)-induced contraction of aortas in Ca2(+)-free medium. 2. This inhibitory effect was completely antagonized by pretreatment with methylene blue. 3. Nicorandil and cromakalim also inhibited the NA-induced contraction of aortas in Ca2(+)-free medium. 4. The inhibitory effects of nicorandil, but not those of cromakalim, were partially antagonized by pretreatment with methylene blue. 5. The methylene blue-insensitive effects of nicorandil and the effects of cromakalim were antagonized by pretreatment with glibenclamide. 6. These results indicate that the inhibitory effect of CD-349 and nicorandil on NA-induced contraction of aortic strips in Ca2(+)-free medium is mediated through increased levels of cyclic GMP. 7. Furthermore, the inhibitory effect of cromakalim and the partial inhibitory mechanism of nicorandil may be mediated through glibenclamide-sensitive K(+)-channels.