Communal C, Ribuot C, Durand A, Demenge P
Laboratoire de Pharmacologie Cardiovasculaire Expérimentale-Biomolécules (PCEBM), Faculté de Pharmacie, Université Joseph Fourier-Grenoble I, La Tronche, France.
Fundam Clin Pharmacol. 1998;12(4):411-9. doi: 10.1111/j.1472-8206.1998.tb00965.x.
The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac volume overload. Aortocaval shunt (ACS) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoproterenol dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index were evaluated in plasma and heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol, and the beta(1)/beta(2)-adrenoceptor ratio were estimated. Four weeks of cardiac volume overload resulted in a 55% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 3.9 +/- 0.1 mg/g in sham and ACS rats, respectively) and a 20% increase in protein contents (from 11.3 +/- 0.7 to 13.8 +/- 1.1 mg/100 mg ventricles in sham and ACS rats, respectively). Furthermore, NA and A concentrations and NA turn-over index were increased in ACS rats (14, 40 and 80% versus sham, respectively). A shift to the right of the responses in heart rate, left ventricular systolic pressure, +dP/dtmax and -dP/dtmax responses following increasing doses of isoproterenol was observed, without change in the dose inducing maximum effect. Total beta-adrenoceptor characteristics and beta(1)/beta(2) ratio were unchanged. However, beta(1)-adrenoceptor density increased in epicardium while decreasing in endocardium of left ventricle from ACS rats. Rightward shift at lower doses of isoproterenol-induced cardiac responses in volume-overloaded rats are not likely due to overall beta-adrenoceptor density changes.
本研究的目的是评估经历4周心脏容量超负荷的动物心肌β-肾上腺素能反应性的变化。对雄性Wistar大鼠进行主动脉腔静脉分流术（ACS）或假手术（假手术组），4周后，在脊髓毁损后研究异丙肾上腺素的剂量效应（变时性、变力性和舒张性特性）。评估血浆和心室中的去甲肾上腺素（NA）和肾上腺素（A）浓度以及NA周转指数，同时用[125I]碘氰吲哚洛尔评估心室匀浆和切片中的β-肾上腺素能受体特性，并估算β(1)/β(2)-肾上腺素能受体比率。4周的心脏容量超负荷导致心室重量/体重比增加55%（假手术组和ACS大鼠分别从2.5±0.1增加到3.9±0.1mg/g），蛋白质含量增加20%（假手术组和ACS大鼠分别从11.3±0.7增加到13.8±1.1mg/100mg心室）。此外，ACS大鼠的NA和A浓度以及NA周转指数增加（分别比假手术组高14%、40%和80%）。观察到随着异丙肾上腺素剂量增加，心率、左心室收缩压、+dP/dtmax和-dP/dtmax反应向右移位，而诱导最大效应的剂量没有变化。总β-肾上腺素能受体特性和β(1)/β(2)比率未改变。然而，ACS大鼠左心室外膜的β(1)-肾上腺素能受体密度增加，而内膜的β(1)-肾上腺素能受体密度降低。容量超负荷大鼠中较低剂量异丙肾上腺素诱导的心脏反应向右移位不太可能是由于整体β-肾上腺素能受体密度变化。
