Effects of ryanodine and 9,21-didehydroryanodine on caffeine-induced contraction of rat and guinea pig aortae.

We compared the effects of ryanodine and 9,21-didehydroryanodine (DH-ryanodine), which are present in commercial preparations of 'ryanodine', on the contractions of rat and guinea pig aortae induced by 20 mM caffeine and tested the dependence of the action of each substance on external Ca2+. With the first protocol, the aortae were incubated with ryanodine or DH-ryanodine for 20 min in Ca2(+)-containing medium, and caffeine was added at 2 min incubation in Ca2(+)-free medium. With the second protocol, each substance was added when the external medium was changed to Ca2(+)-free medium, and 20 min later, caffeine was applied. Ryanodine and DH-ryanodine inhibited the caffeine-induced contractions in a similar way; i.e., with maximal effects at 3 microM and lesser effects at 10 microM. The potencies of inhibition by both substances were similar except that the effect of ryanodine at 1.5 microM was more potent than that of DH-ryanodine with the second protocol. The response by muscles previously loaded with Ca2+ to a second application of caffeine was more greatly inhibited by both compounds (use-dependent effect). The inhibition of the contraction due to the first or second application of caffeine was greater when either agent was applied in Ca2+-containing medium than in Ca2(+)-free medium. These results indicate that ryanodine and DH-ryanodine are similar in their effects on caffeine-induced Ca2+ release in vascular smooth muscle and that cellular Ca2+ levels may affect the action of ryanodine.