Becker D M, Romano F D, Scanlon P J, Jones S B, Euler D E
Department of Medicine, Loyola University Medical Center, Maywood, Ill.
Pharmacology. 1988;36(3):172-82. doi: 10.1159/000138381.
To test the hypothesis that beta-receptors 'up-regulate' during chronic beta-blockade, myocardial beta-receptor density, affinity and functional sensitivity were examined in dogs before and after chronic beta-blockade. Membrane preparations from the left ventricle and right atrium were assayed for beta-receptors in 8 control dogs, and 8 dogs given oral nadolol (4 mg/kg) twice a day for 3 weeks. Beta-receptor density and affinity of membrane fractions were determined using 3H-dihydroalprenolol (0.5-20 nM), and Scatchard analysis. Beta-receptor densities after chronic beta-blockade were 419 +/- 28 (mean +/- SEM) and 436 +/- 47 fmol/mg protein in membranes from the left ventricle and right atrium respectively. These values were not significantly different from the left ventricle (412 +/- 25) or the right atrium (413 +/- 25) in control dogs. Beta-receptor affinities were 5.6 +/- 0.5 nM (left ventricle) and 8.5 +/- 1.1 nM (right atrium) after chronic beta-blockade, and not significantly different from control (6.9 +/- 0.7 nM, ventricle; 11.3 +/- 0.9 nM, atrium). Beta-receptor sensitivity was determined in membrane fractions from the left ventricle by analysis of the dose-response relationship between isoproterenol and the formation of c-AMP (pmol/min/mg protein). The concentration of isoproterenol that resulted in 50% of the maximal response was not significantly altered by chronic beta-blockade. Maximally stimulated adenylate cyclase with Gpp(NH)p or NaF was also unchanged by beta-blockade. These results suggest that in the canine heart, chronic beta-blockade does not lead to 'up-regulation' of beta-receptors nor catecholamine supersensitivity.
为验证慢性β受体阻滞剂治疗期间β受体“上调”这一假说，研究人员检测了犬在慢性β受体阻滞剂治疗前后心肌β受体密度、亲和力及功能敏感性。对8只对照犬以及8只每天口服两次纳多洛尔（4毫克/千克），持续3周的犬，测定其左心室和右心房膜制剂中的β受体。使用3H-二氢阿普洛尔（0.5 - 20纳摩尔）及Scatchard分析来测定膜组分的β受体密度和亲和力。慢性β受体阻滞剂治疗后，左心室和右心房膜中的β受体密度分别为419±28（平均值±标准误）和436±47飞摩尔/毫克蛋白。这些数值与对照犬左心室（412±25）或右心房（413±25）相比无显著差异。慢性β受体阻滞剂治疗后，β受体亲和力在左心室为5.6±0.5纳摩尔，右心房为8.5±1.1纳摩尔，与对照（心室6.9±0.7纳摩尔；心房11.3±0.9纳摩尔）相比无显著差异。通过分析异丙肾上腺素与环磷酸腺苷（c-AMP）生成（皮摩尔/分钟/毫克蛋白）之间的剂量反应关系，测定左心室膜组分中的β受体敏感性。慢性β受体阻滞剂治疗未显著改变产生最大反应50%时的异丙肾上腺素浓度。用Gpp(NH)p或NaF最大程度刺激的腺苷酸环化酶也未因β受体阻滞剂而改变。这些结果表明，在犬心脏中，慢性β受体阻滞剂治疗不会导致β受体“上调”，也不会引起儿茶酚胺超敏反应。
