beta(3)-Adrenoceptor-mediated responses in diabetic rat heart

Abstract

beta 3-adrenoceptors mediate negative inotropic effect in contrast to classical beta(1)- and beta(2)-adrenoceptors. Cardiac (beta(3)-adrenoceptors are upregulated in experimental diabetes. Thus, cardiodepressant effect mediated by beta(3)-adrenoceptors has been proposed to contribute to the impaired cardiac function in this pathology. In our study, we investigated the influence of streptozotocindiabetes on cardiac contractility to beta(3)-adrenoceptors stimulation by using Langendorff-perfused rat hearts. BRL 37344, a selective (beta(3)-adrenoceptor agonist, induced dose-dependent decreases in left ventricular developed pressure (LVDP) in hearts from control rats. BRL 37344 also dose-dependently decreased +dP/dt and -dP/dt values. Effects of BRL 37344 were abolished by SR 59230, but not altered by nadolol pre-treatment. On the other hand, these effects of BRL 37344 were all significantly increased in hearts from diabetic rats. We also observed that diabetes significantly increased the mRNA levels encoding cardiac beta(3)-adrenoceptors. In addition, Gi(alpha 2) mRNA expressions were found to be increased in the cardiac tissue of diabetic rats as well. The effect of BRL 37344 on cardiac contractility was normalized upon treatment of diabetic rats with insulin. These data demonstrate an increased effect of beta(3)-adrenoceptor stimulation on hemodynamic function of the heart in accordance with an increased mRNA levels encoding cardiac beta(3)-adrenoceptors in 8-week diabetic rats.