Chronotropic effects of histamine and dimaprit were studied in the conscious dog with chronic atrioventricular block. Histamine at 0.2-5 micrograms/kg and dimaprit at equimolar doses (i.e. 0.25-6.25 micrograms/kg) increased atrial rate dose-relatedly. Blockade of muscarinic receptors reduced these effects and simultaneous blockade of muscarinic and beta-adrenergic receptors abolished them. Histamine and dimaprit moderately increased ventricular rate. Blockade of muscarinic receptors did not modify these effects, but blockade of beta-adrenoceptors with or without simultaneous blockade of muscarinic receptors suppressed them. After blockade of beta-adrenoceptors, histamine and more rarely dimaprit sometimes decreased atrial and ventricular rates. These effects were prevented by additional muscarinic blockade. Histamine and dimaprit lowered mean blood pressure to the same degree before and after each antagonist. The positive chronotropic effects of histamine and dimaprit, at these doses, are probably reflex responses to their hypotensive effects. The negative chronotropic effects of histamine after pindolol are due to muscarinic receptor activation. No evidence was found to implicate histamine-specific receptors in any of the chronotropic effects of histamine and dimaprit.
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