α1a-Adrenergic receptor mediated positive chronotropic effect in right atria isolated from rats

Abstract

Experiments in right atria isolated from adult male rats were designed to determine which of the α1-adrenergic receptor (α1-AR) subtypes are involved in the positive chronotropic effect of phenylephrine, an α1-AR agonist. Chloroethylclonidine (CEC), an irreversible α1b-, α1c-, and α1d-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 α1a- and α1c-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 α-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 β-adrenergic agonist isoproterenol was not affected by CEC, WB4101, or phenoxybenzamine. These data suggest that the positive chronotropic effect of α1-adrenergic agonists in rat right atria is mediated via stimulation of α1a-ARs.Key words: α1-adrenergic receptor subtypes, chloroethylclonidine, WB4101, phenylephrine, right atria (rat).