Anthonio R L, Brodde O E, van Veldhuisen D J, Scholtens E, Crijns H J, van Gilst W H
Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Int J Cardiol. 2000 Jan 15;72(2):137-41. doi: 10.1016/s0167-5273(99)00181-3.
Beta-adrenoceptor density is altered in different cardiac diseases. In heart failure beta-adrenoceptor density is down regulated but in acute myocardial ischemia beta-adrenoceptor density is up regulated. In hearts with myocardial infarction total beta-adrenoceptor density is decreased shortly after myocardial infarction.
To investigate whether total beta-adrenoceptor number is altered in the chronic phase after myocardial infarction, and to identify the specificity of alteration, we studied male Wistar rats (n = 18) which underwent a ligation of the left coronary artery or a sham operation. Twelve weeks after coronary ligation, rats were sacrificed and hearts were excised, perfused to obtain blood-free myocardium and frozen in liquid nitrogen. Infarcted myocardium was identified visually and separated from non-infarcted myocardium. Total beta-adrenoceptor number was calculated in fmol (-)-[125I]iodocyanopindolol specifically bound/mg protein and the relative amount of beta1- and beta2-adrenoceptor density was measured by inhibition of (-)-[125I]iodocyanopindolol binding with CGP 20712 A.
Total beta-adrenoceptor number in infarcted myocardium was significantly decreased (25.7+/-1.4 vs. 24.9+/-2.2 vs. 20.1+/-3.2 fmol/mg protein (P=0.03) resp. Sham vs. Non-infarcted vs. Infarcted myocardium), due to a decrease of only beta1-adrenoceptor density (14.7+/-0.61 vs. 12.7+/-1.09 vs. 4.84+/-0.96 fmol/mg protein (P=0.004) resp.), whereas the beta2-adrenoceptor density and the dissociation constant (Kd) were not significantly decreased.
In the infarcted myocardium total beta-adrenoceptor density is decreased due to a decreased beta1-adrenoceptor density at 12 weeks after myocardial infarction.
β-肾上腺素能受体密度在不同的心脏疾病中会发生改变。在心力衰竭中，β-肾上腺素能受体密度下调，但在急性心肌缺血中，β-肾上腺素能受体密度上调。在心肌梗死的心脏中，心肌梗死后不久总β-肾上腺素能受体密度会降低。
为了研究心肌梗死后慢性期总β-肾上腺素能受体数量是否改变，并确定改变的特异性，我们研究了接受左冠状动脉结扎或假手术的雄性Wistar大鼠（n = 18）。冠状动脉结扎12周后，处死大鼠，取出心脏，灌注以获得无血心肌并在液氮中冷冻。通过肉眼识别梗死心肌并将其与非梗死心肌分离。以每毫克蛋白质特异性结合的fmol（-）-[125I]碘氰吲哚洛尔计算总β-肾上腺素能受体数量，并通过用CGP 20712 A抑制（-）-[125I]碘氰吲哚洛尔结合来测量β1-和β2-肾上腺素能受体密度的相对量。
梗死心肌中的总β-肾上腺素能受体数量显著降低（假手术组、非梗死心肌组和梗死心肌组分别为25.7±1.4、24.9±2.2和20.1±3.2 fmol/mg蛋白质（P = 0.03）），这是由于仅β1-肾上腺素能受体密度降低（分别为14.7±0.61、12.7±1.09和4.84±0.96 fmol/mg蛋白质（P = 0.004）），而β2-肾上腺素能受体密度和解离常数（Kd）没有显著降低。
在心肌梗死后12周，梗死心肌中的总β-肾上腺素能受体密度降低是由于β1-肾上腺素能受体密度降低所致。
