Functional studies on α1‐adrenoceptor subtypes mediating inotropic effects in rat right ventricle

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Abstract
1 We have studied the α1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. (α1A-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases. 2 Treatment with chloroethylclonidine did not affect the maximal β-adrenoceptor-mediated inotropic effects in rat right ventricle or the maximal α1A-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 α-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 α1B-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 α1A-adrenoceptor-selective antagonists, 5-methylurapidil and (±)-tamsulosin, demonstrated that adrenaline causes its inotropic effects mainly via the α1B-adrenoceptor subtype. Schild analysis of 5-methyl-urapidil inhibition experiments in chloroethylclonidine-treated ventricles indicated that only α1A-adrenoceptors mediate the inotropic effects of adrenaline following inactivation of the α1B-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 α1B-adrenoceptors via release of Ca2+ from an intracellular pool. Following inactivation of α1B-adrenoceptors by chloroethylclonidine treatment, α1A-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 α1B-adrenoceptors exert a tonic inhibitory effect on α1A-adrenoceptors.