Tawfik-Schlieper H, Moll M, Schmid B, Schwinger R H, Paul M, Ganten D, Böhm M
Klinik III für Innere Medizin der Universität zu Köln, Germany.
Clin Exp Hypertens. 1995 May;17(4):631-48. doi: 10.3109/10641969509037413.
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.
在本研究中，我们研究了α-和β-肾上腺素能受体介导的对心肌收缩力的影响（在普萘洛尔存在的情况下使用去氧肾上腺素和异丙肾上腺素）以及受体密度（使用[³H]-哌唑嗪和[¹²⁵I]-碘氰吲哚洛尔进行结合研究），以高血压转基因大鼠（TGR(mREN2)27）和年龄匹配的Sprague-Dawley大鼠（SP）作为对照。在TGR(mREN2)27中，异丙肾上腺素和去氧肾上腺素的正性肌力作用减弱，而Ca²⁺的作用未改变。两组的半数有效浓度值无差异。在转基因大鼠肥厚的左心室中观察到β-肾上腺素能受体下调，推测这与β-肾上腺素能受体介导的正性肌力作用减弱有关。α-肾上腺素能受体密度增加，这可能是β-肾上腺素能途径有效性受损的一种代偿机制。然而，由于α-肾上腺素能受体激动剂的作用未增强反而减弱，α-肾上腺素能受体与受体后事件的解偶联可能在观察到的效应中起作用。
