Alpha 1-adrenoceptor stimulation reduced the positive chronotropic effect of simultaneously administered beta-adrenoceptor- and H2-receptor agonists in guinea-pig right atria.

The modulatory influence of alpha 1-adrenoceptor agonists on the beta-adrenoceptor-mediated or H2-receptor-mediated positive chronotropic effect was investigated in isolated guinea-pig right atria. In the presence of cirazoline, the isoprenaline- or impromidine-induced positive chronotropic effect was significantly reduced. Methoxamine also reduced the isoprenaline-induced positive chronotropic effect. The reduction was abolished by the alpha 1-adrenoceptor antagonist prazosin. The protein kinase C activator phorbol-12-myristate-13-acetate, as well as the protein kinase inhibitor polymyxin B, had no influence on the cirazoline-evoked decrease of the beta-adrenoceptor-mediated positive chronotropic effect. Cirazoline, in the absence of isoprenaline or impromidine, concentration-dependently decreased heart rate, which could not be abolished by phentolamine and prazosin. Stimulation of alpha 1-adrenoceptors by phenylephrine in the presence of the beta-adrenoceptor antagonist sotalol, decreased spontaneous heart rate. The decrease was abolished by prazosin as well as by pretreatment with the neurotoxin 6-hydroxy-dopamine. The decrease in heart rate may to some extent be the result of interactions at the level of signal transduction systems of the 3 receptors.