Alterations of cardiac alpha- and beta-adrenoceptors and inotropic responsiveness in hypertensive transgenic rats harbouring the mouse renin gene (TGR(mREN2)27).

In the present study, we investigated the alpha- and beta-adrenoceptor-mediated effects on myocardial force of contraction (using phenylephrine in the presence of propranolol and isoprenaline) and receptor densities (binding studies using [3H]-prazosin and [125I]-iodocyanopindolol) in hypertensive transgenic rats (TGR(mREN2)27) and age-matched Sprague-Dawley rats (SP) as controls. In TGR(mREN2)27 the positive inotropic effects of isoprenaline and phenylephrine were reduced, while the effect of Ca2+ was unchanged. The EC50-values did not differ in both groups. A down-regulation of the beta-adrenoceptors was observed in the hypertrophied left ventricles of transgenic rats, which is postulated to be involved in the reduced beta-adrenoceptor-mediated positive inotropic effect. The alpha-adrenoceptor density was increased, which could represent a compensatory mechanism for the impaired effectiveness of the beta-adrenergic pathway. However, since the effect of alpha-adrenoceptor agonist is not enhanced but even reduced, an uncoupling of alpha-adrenoceptors from post receptor events could play a role in the observed effects.