Αlpha_1B-adrenoceptor-mediated positive inotropic and positive chronotropic actions in the mouse atrium

Modulation of cardiac contractility by α-adrenoceptor is well known in several mammals. Mice are useful experimental animals, but α-adrenoceptor-mediated responses have been examined only in the ventricles. To determine function of α-adrenoceptors in the atrium, effects of α-adrenoceptor agonists on spontaneous contraction and electrical-field stimulation (EFS)-induced contraction were examined. In addition, expression of α_1A, α_1B, α_1D and β₁-adrenoceptor mRNAs were examined. In the right atrium, noradrenaline and phenylephrine caused positive inotropic and positive chronotropic actions. However, methoxamine, clonidine and xylazine caused positive inotropic actions, but contractile frequency was decreased at high concentrations. Phenylephrine-induced positive inotropic and chronotropic actions were partially decreased by propranolol, and both actions remained in the presence of propranolol were inhibited by phentolamine or prazosin. A low concentration of silodosin (<100 nM) did not but a high concentration (1 μM) decreased the phenylephrine-induced chronotropic actions. Negative chronotropic actions of clonidine and xylazine were insensitive to propranolol and phentolamine. The EFS-induced contraction of the left atrium was potentiated by noradrenaline, phenylephrine and methoxamine but was not changed by clonidine or xylazine. Propranolol partially decreased the actions of phenylephrine, and prazosin caused additional inhibition. Expression of β₁-, α_1A-_, α_1B- and _α1D-adrenoceptor mRNAs was found in the atrium, and the expression level of β₁-adrenoceptor was the highest. Of α₁-adrenoceptors, the expression level of α_1B was higher than that of α_1A and α_1D. In conclusion, α_1B-adrenoceptors are expressed in the mouse atrium and mediate both positive chronotropic and inotropic actions. In contrast, the α₂-adrenoceptor is not functional in the isolated atrium.