Communal C, Ribuot C, Durand A, Demenge P
Laboratoire de Pharmacologie Cardiovasculaire Expérimentale-Biomolécules (PCEBM), UFR de Pharmacie Université Joseph Fourier Grenoble I, La Tronche, France.
Fundam Clin Pharmacol. 1998;12(6):590-8. doi: 10.1111/j.1472-8206.1998.tb00991.x.
The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac pressure-overload. Abdominal aortic constriction (AAC) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoprenaline dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index (DHPG /NE ratio) were evaluated in 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 pressure overload resulted in a 70% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 4.2 +/- 0.3 mg/g in sham and AAC rats, respectively) and a 24% increase in protein contents (from 11.3 +/- 0.7 to 14.0 +/- 1.1 mg/100 mg ventricle in sham and AAC rats respectively). The ventricle NA content was similar in AAC and sham, while the ventricle A content and NA turn-over index were significantly increased in AAC rats (35 and 80% vs sham, respectively). Dose response of isoprenaline was significantly shifted to the right for all studied effects in AAC rats. However, maximal response (in relative values) was similar in AAC and sham rats only for heart rate but not for parameters depending on left ventricle contractile response. The beta-adrenoceptor density was significantly decreased in AAC by 30% without apparent affinity change and due to decreases in beta (1)-sites in septum and to beta (1)- and beta (2)-adrenoceptors in left ventricle endocardium. Decreases in isoprenaline-induced cardiac responses in AAC rats are associated with beta (1)-adrenoceptor density reduction and modification of beta (1)- and beta (2)-adrenoceptor ratio. These modifications are not the only reason for such dose response changes, at least for contractile response.
本研究的目的是评估经历4周心脏压力超负荷的动物心肌β-肾上腺素能反应性的变化。对雄性Wistar大鼠进行腹主动脉缩窄（AAC）或假手术（sham），4周后，在脊髓破坏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（DHPG/NE比值），同时用[125I]碘氰吲哚洛尔评估心室匀浆和切片中的β-肾上腺素能受体特征以及β(1)/β(2)-肾上腺素能受体比值。4周的心脏压力超负荷导致心室重量/体重比增加70%（假手术组和AAC组大鼠分别从2.5±0.1增加到4.2±0.3mg/g），蛋白质含量增加24%（假手术组和AAC组大鼠分别从11.3±0.7增加到14.0±1.1mg/100mg心室）。AAC组和假手术组的心室NA含量相似，而AAC组大鼠的心室A含量和NA周转指数显著增加（分别比假手术组高35%和80%）。对于AAC组大鼠所有研究的效应，异丙肾上腺素的剂量反应显著右移。然而，仅心率的最大反应（相对值）在AAC组和假手术组大鼠中相似，而依赖于左心室收缩反应的参数则不同。AAC组中β-肾上腺素能受体密度显著降低30%，亲和力无明显变化，这是由于室间隔中β(1)位点以及左心室内膜中β(1)和β(2)肾上腺素能受体减少所致。AAC组大鼠中异丙肾上腺素诱导的心脏反应降低与β(1)-肾上腺素能受体密度降低以及β(1)和β(2)-肾上腺素能受体比值改变有关。这些改变不是这种剂量反应变化的唯一原因，至少对于收缩反应不是。
