Alpha 1A- and alpha 1B-adrenoceptor-mediated positive chronotropic effects on isolated rat atrium.

The positive chronotropic effect of alpha 1-adrenoceptor subtypes was studied on the isolated right atrium of adult male Wistar rats. In the presence of beta-blocker propranolol, chloroethylclonidine (Chl) (an irreversible alpha 1B inactivator) reduced the positive chronotropic effect of phenylephrine (Phe). When the basal rate was lowered by cholinergic stimulation. Chl showed less effect on the increase of spontaneous beat rate. H-7, a protein kinase C (PKC) inhibitor, lowered the chronotropic effect to Phe under physiological condition, but did not affect the Phe-induced positive chronotropic effect when basal rate was lessened by carbachol. These suggested that the chronotropic effect was mainly mediated by alpha 1B receptors, and partially related to the activation of PKC by second messengers under physiological conditions. The compensatory effect of the alpha 1-adrenoceptors was mainly mediated by alpha 1A receptors, which is scarcely involved in the activation of PKC.