Actions and interactions of dihydropyridines and ethanol on the rat sinus node
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°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 dosedependent 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 (1.8×10−2 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 (5.3×10−2 M) did not by itself affect the SNR, but it antagonized the chronotropic actions of the two DHPs.
Key Wordssinus node automaticity cardiac rhythm dihydropyridines ethanol calcium modulators calcium antagonists calcium agonists drug interactions
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