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.
Williamson
A P
AP
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Seifen
E
E
Lindemann
J P
JP
Kennedy
R H
RH
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; D010656:Phenylephrine; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine