Yahagi M, Honda T, Mizumachi K, Tezuka S, Okada K
Department of Anesthesiology, Teikyo University School of Medicine.
Kokyu To Junkan. 1991 Dec;39(12):1209-14.
We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines. [METHODS] Twenty-nine Japanese White rabbits were divided into 2 groups. Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E. coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17). BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study. We used [3H] dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol. B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist. In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts. [RESULTS] In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM). MAP and HR were slightly decreased in E-LPS but not significantly. Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM). Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected. In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines. [CONCLUSION] These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock.
我们研究了内毒素或细胞因子诱导的高动力状态下心肌β-肾上腺素能受体（BAR）和β1-肾上腺素能受体（B1AR）数量的变化。[方法] 29只日本白兔分为2组。腹腔注射无菌生理盐水（SAL）或大肠杆菌内毒素（LPS；50微克/千克）18小时后取出心脏（E组，n = 12），或静脉注射SAL或细胞因子（白细胞介素1-β；5微克/千克，随后以25纳克/千克/分钟的速度注射2小时，或肿瘤坏死因子；5微克/千克）3小时后取出心脏（C组，n = 17）。采用放射性配体结合研究技术测定兔左心室心肌膜中的BAR和B1AR数量。我们使用[3H]二氢阿普洛尔（3H-DHA）作为放射性配体，3H-DHA与BARs的特异性结合定义为存在和不存在10微摩尔普萘洛尔时的差异。通过在高选择性β2-肾上腺素能受体拮抗剂ICI 118,551（5×10^(-8) M）存在下3H-DHA的特异性结合来评估B1AR数量。在E组中，在心脏切除前，于戊巴比妥钠麻醉下测量平均动脉血压（MAP）、心率（HR）和心输出量（CO）（通过热稀释法）。[结果] 在E组中，与注射SAL的兔子（E-SAL）相比，注射LPS的兔子（E-LPS）的心输出量显著增加（p < 0.05）（E-LPS；0.75 ± 0.02升/分钟，E-SAL；0.61 ± 0.05升/分钟，平均值 ± 标准误）。E-LPS组的MAP和HR略有下降，但无统计学意义。与E-SAL组相比，E-LPS组心肌膜中3H-DHA与BARs的最大结合量（Bmax）显著降低（p < 0.05），降低了18%（E-LPS；48.2 ± 4.3飞摩尔/毫克蛋白，E-SAL；58.9 ± 2.9飞摩尔/毫克蛋白，平均值 ± 标准误）。同样，E-LPS组中3H-DHA与B1ARs的Bmax降低了18%，尽管未检测到统计学意义。在C组中，给予细胞因子3小时后，BAR和B1AR数量均略有下降，但无统计学意义。[结论] 这些数据表明，在内毒素休克的高动力阶段可能会发生心脏BARs的下调。
