Alterations of Cardiac α- and β-Adrenoceptors and Inotropic Responsiveness in Hypertensive Transgenic Rats Harbouring the Mouse Renin Gene (TGR(mREN2)27)

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Abstract
In the present study, we investigated the α- and β-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 β-adrenoceptors was observed in the hypertrophied left ventricles of transgenic rats, which is postulated to be involved in the reduced β-adrenoceptor-mediated positive inotropic effect. The α-adrenoceptor density was increased, which could represent a compensatory mechanism for the impaired effectiveness of the β-adrenergic pathway. However, since the effect of α-adrenoceptor agonist is not enhanced but even reduced, an uncoupling of α-adrenoceptors from post receptor events could play a role in the observed effects.