title: Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle.
abstract: 1. We have studied the alpha 1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. alpha 1A-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases. 2. Treatment with chloroethylclonidine did not affect the maximal beta-adrenoceptor-mediated inotropic effects in rat right ventricle or the maximal alpha 1A-adrenoceptor-mediated contractile effects in rat vas deferens; it did not alter the potency of isoprenaline in the ventricle and reduced the potency of the alpha-adrenoceptor antagonists in vas deferens only slightly. Treatment of right ventricular strips with CdCl2 markedly reduced resting tension and enhanced maximal inotropic effects of isoprenaline but did not affect its potency. 3. Inactivation of cardiac alpha 1B-adrenoceptors by treatment with chloroethylclonidine slightly enhanced the maximal inotropic effects of the full agonist, adrenaline and of several partial agonists. 4. Schild analysis of inhibition experiments with the alpha 1A-adrenoceptor-selective antagonists, 5-methyl-urapidil and (+/-)-tamsulosin, demonstrated that adrenaline causes its inotropic effects mainly via the alpha 1B-adrenoceptor subtype. Schild analysis of 5-methyl-urapidil inhibition experiments in chloroethylclonidine-treated ventricles indicated that only alpha 1A-adrenoceptors mediate the inotropic effects of adrenaline following inactivation of the alpha 1B-adrenoceptors. 5. In control ventricles the organic Ca2+ entry blocker, nitrendipine and treatment with the inorganic Ca2+ entry blocker, CdCl2 did not reduce inotropic effects of adrenaline whereas ryanodine treatment inhibited them. In contrast, nitrendipine and CdCl2 treatment had major inhibitory effects in chloroethylclonidine-treated but lacked inhibitory effects in phenoxybenzamine-treated ventricular strips. 6. We conclude that inotropic effects of adrenaline in rat heart are mediated mainly by alpha 1B-adrenoceptors via release of Ca2+ from an intracellular pool. Following inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment, alpha lA-adrenoceptors can fully compensate and mediate inotropic effects by promoting influx of extracellular Ca2+ at least partly via voltage-operated channels.Therefore, we speculate that alpha 1B-adrenoceptors exert a tonic inhibitory effect on alpha 1A-adrenoceptors.
authors.affiliation: Department of Medicine, University of Essen, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
authors.forename: G
authors.initials: G
authors.lastname: Hanft
authors.forename: G
authors.initials: G
authors.lastname: Gross
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002712:Chlorides; D018340:Receptors, Adrenergic, alpha-1; D002104:Cadmium; C051731:chlorethylclonidine; D009568:Nitrendipine; D019256:Cadmium Chloride; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine