Actions and interactions of dihydropyridines and ethanol on the rat sinus node

Abstract

The actions and interactions of dihydropyridines (DHPs) and ethanol on sinus node (SN) automaticity were studied using rat sinoatrial preparations superfused with Tyrode's solution at 37 degrees C. Intracellular microelectrodes were used to monitor SN rate (SNR). The automaticity of the SN was not affected by nimodipine 10(-10) M, but it was depressed by a higher concentration of this calcium antagonist (10(-8) M). The racemic compound (+/-)Bay K 8644 had a dose-dependent biphasic chronotropic action: At 10(-8) M it decreased the SNR, while at 10(-7) M it increased the SNR. The negative component was blocked by atropine. A small concentration of ethanol (1.8 x 10(-2) M) had a positive chronotropic effect on the SN, and this action was blocked by nimodipine 10(-10) M. This small concentration of ethanol did not modify the chronotropic effects of either of the DHPs. A higher concentration of ethanol (5.3 x 10(-2) M) did not by itself affect the SNR, but it antagonized the chronotropic actions of the two DHPs.

Effects of calcium channel agonism by Bay-K-8644 on ventricular fibrillation threshold of isolated heart

“…These changes would be consonant with the concept that Bay-K-8644 can prolong the open state of the calcium channel [20]. Bay-K-8644 has a positive inotropic effect [17,20,21] and at concentrations above 10 -s M a stimulatory effect on the sinus node [22]. These observations all follow from the basic effect of Bay-K-8644 to increase calcium influx via the calcium channel.…”