Abstract
The effects of imipramine on sinoatrial rate and chronotropic responses to transmural stimulation (TS) were studied in the isolated guinea-pig right atrial preparation. The negative chronotropic response (cholinergically mediated rate decrease) to TS was progressively inhibited by imipramine (5 x 10(-6) M). This inhibition can be attributed directly to an "atropine-like" effect of this drug. The positive chronotropic response (adrenergically mediated rate increase) to TS was markedly potentiated by imipramine at similar therapeutic doses; higher doses (5 x 10(-5) M) substantially depressed this rate response. This depression of the adrenergic response to TS does not appear to be the result of a blockade of beta adrenergic receptors since imipramine still potentiated the rate increase in response to exogenous norepinephrine at doses where no TS response remained. Basal spontaneous rate was also depressed by imipramine at high doses (5 x 10(-5) M), both in the absence and presence of autonomic blockers.
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