Effect of Nifedipine on the Contractile Response in the Isolated Rat Phrenic - Hemidiaphragm

Choi, Yu Sun; Kim, Tai Yo

Abstract

The effects of nifedipine, a dihydropyridine Ca2+ antagonist, on the eleetrically-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat hemidiaphragm preparation. Nifedipine, in concentrations ranging from 3 to 100 uM, increased the electrically-evoked (nerve stimulation, 0.1 Hz, 0.5 ms, 10 V) twitch response and train-of-four ratio in a dose-relat- ed fashion, and the potentiating effects were inhibited by d-tubocurarine preteratment. The effect of nifedipine was not affected by reducing the extracellular Ca2+ concentration from 2.5 mM to 1.25 mM. In cases of the direct(muscle, 0.1 Hz, 5 ms, 10 V) stimulation, nifedipine increased the twitch response in a dose-dependent manner, but the amplitudes were smaller than those in indirect stimulation. Nifedipine 30 uM potentiated the contractile response induced by 70 mM KC1 and caffeine(10 mM)-induced isometric contractile responses were markedly potentiated by nifedipine treatmeat. Nifedipine 70 upotentiated the effect of l mM caffeine on the electrically-evoked twitch response and the potentiating effect was also seen in reverse treatment. On the basis of these findings, the result of present study suggests that the potentiating contractile response by nifedipine is mediated by two distinctive mechanisms. One is the acetylcholine release from presynaptic nerve terminal and the other may be due to the releases of Ca2+ in sarcoplasmic reticulum.