The effect of diazepam on ventricular automaticity induced by a local injury. Evidence of involvement of "peripheral type" benzodiazepine receptors.

The effect of diazepam on ectopic cardiac automaticity has been examined in rats. We also investigated whether "central" or "peripheral type" benzodiazepine receptors are involved, as well as the role of calcium, on the possible effect of diazepam, by studying the interaction of this drug with either GABA, picrotoxin, RO 15-1788, PK 11195, diltiazem or Bay K 8644. A local injury of the rat isolated right ventricle produced a sustained abnormal rhythm which was completely abolished by diazepam (30-50 microM). This effect was not modified by the presence of either GABA (100 microM) picrotoxin (2 microM) or RO 15-1788 (5 microM) but it was reduced by the antagonist of "peripheral type" benzodiazepine receptors PK 11195 (0.1 microM). On the other hand the calcium channel blocker diltiazem (5 microM) and the calcium channel activator Bay K 8644 (3 nM), respectively, potentiated and reduced the effect of diazepam. It is concluded that diazepam effectively reduces ectopic cardiac automaticity in the rat. The "central type" benzodiazepine receptors are not involved in this effect, but it seems to be, at least, partially mediated by "peripheral type" receptors and is a calcium-dependent phenomenon.