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 phenylephrine, an alpha 1-AR agonist. Chloroethylclonidine (CEC), an irreversible alpha 1b-, alpha 1c-, and alpha 1d-AR antagonist, did not alter the efficacy or potency of phenylephrine; however, CEC did elicit a concentration-dependent negative chronotropic effect and reduce the absolute maximum spontaneous rate observed in the presence of phenylephrine. WB4101, a competitive alpha 1a- and alpha 1c-AR-selective antagonist, did not alter basal spontaneous rate or the efficacy of phenylephrine, but it did produce a significant rightward shift of the phenylephrine concentration-response curve. Phenoxybenzamine, an irreversible nonselective alpha-AR antagonist, elicited a concentration-dependent negative chronotropic effect, a significant rightward shift of the phenylephrine concentration-response curve, and a reduction in the efficacy of phenylephrine. The chronotropic action of the beta-adrenergic agonist isoproterenol was not affected by CEC, WB4101, or phenoxybenzamine. These data suggest that the positive chronotropic effect of alpha 1-adrenergic agonists in rat right atria is mediated via stimulation of alpha 1a-ARs.