ALPHA(1A)-ADRENERGIC RECEPTOR-MEDIATED POSITIVE CHRONOTROPIC EFFECT IN RIGHT ATRIA ISOLATED FROM RATS

Experiments in right atria isolated from adult male rats were designed to determine which of the alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes are involved in the positive chronotropic effect of phenyleph rine, an alpha(1)-AR agonist. Chloroethylclonidine (CEC), an irreversi ble alpha(1b)-, alpha(1c)-, and alpha(1d)-AR antagonist, did not alter the efficacy or potency of phenylephrine; however, CEC did elicit a c oncentration-dependent negative chronotropic effect and reduce the abs olute maximum spontaneous rate observed in the presence of phenylephri ne. WB4101, a competitive alpha(1a)- and alpha(1c)-AR-selective antago nist, did not alter basal spontaneous rate or the efficacy of phenylep hrine, but it did produce a significant rightward shift of the phenyle phrine concentration - response curve. Phenoxybenzamine, an irreversib le nonselective alpha-AR antagonist, elicited a concentration dependen t negative chronotropic effect, a significant rightward shift of the p henylephrine concentration - response curve, and a reduction in the ef ficacy of phenylephrine. The chronotropic action of the beta-adrenergi c agonist isoproterenol was not affected by CEC, WB4101, or phenoxyben zamine. These data suggest that the positive chronotropic effect of al pha(1)-adrenergic agonists in rat right atria is mediated via stimulat ion of alpha(1a)-ARs.