卡维地洛治疗心力衰竭受体机制的研究

目的研究卡维地洛(CAR)治疗心力衰竭的受体机制。方法应用腹主动脉缩窄法建立大鼠心衰模型。采用Langendorff离体心脏灌流,应用异丙肾上腺素(ISO)、卡维地洛、普奈洛尔(PRL)和特异性的β3肾上腺素受体(β3AR)阻滞剂SR59230A对正常大鼠和心衰大鼠的离体心脏进行灌流,比较各种药物对心功能指标的影响。同时取静脉血测定正常组和心衰组的去甲肾上腺素(NE)水平。结果①心衰组的心功能指标较正常组明显降低,而NE水平则明显高于正常组。②PRL作用于ISO灌流后的离体心脏时,心衰组的左室压力最大上升速率(+dp/dtmax)降低40.37%±2.52%,左室压力最大下降速率(-dp/dtmax)降低41.36%±1.10%;CAR作用于ISO灌流后的离体心脏时,心衰组的+dp/dtmax降低24.73%±3.60%,-dp/dtmax降低22.05%±1.27%,两组比较差异有显著性(P<0.05),结果显示使用CAR后的心功能指标较用PRL后有改善。③CAR作用于离体心脏时,心衰组的+dp/dtmax增加41.57%±14.98%,-dp/dt增加33.39%±6.41%;特异性的β3AR阻滞剂SR59230A作用于心衰的离体心脏时+dp/dtmax增加45.75%±2.64%,-dp/dtmax增加42.81%±9.62%,心功能均有改善,两组比较差异无显著性(P>0.05)。结论CAR治疗心衰的另一种机制可能是通过阻断β3AR发挥作用的。

The receptor mechanism of carvedilol on heart failure

Aim To study the receptor mechanism of carvedilol(CAR) on heart failure.Methods Established rat model of heart failure was induced by abdominal aortic coarctation.With modified Langendorff model of rat,isoproterenol(ISO),carvedilol,propranolol(PRL) and the specific β3 adrenergic receptor(β3AR) blocker SR59230A were given perfusion on heart failure and normal rats' hearts.Then the cardiac function was investigated.At the same time,plasma norepinephrine in normal and heart failure group was measured.Results ① The ±dp/dtmax of heart failure group were significantly reduced compared with those of the normal group,and the norepinephrine level was remarkably higher than that of the normal group.② In heart failure group,perfused PRL on the basis of ISO,the maximum rate of left ventricular pressure rise(+dp/dtmax) decreased by 40.37%± 2.52%,the maximum rate of left ventricular pressure decrease(-dp/dtmax) reduced by 41.36%±1.10%;perfused CAR on the basis of ISO,+dp/dtmax decreased by 24.73%± 3.60%,-dp/dtmax reduced by 22.05%±1.27%.There were differences between these two groups,and the cardiac function perfused CAR was better than PRL.③ Perfused CAR in heart failure group,+dp/dtmax increased by 41.57%±14.98%,-dp/dtmax increased by 33.39%±6.41%;perfused β3AR specific blocker SR59230A,+dp/dtmax increase by 45.75% ±2.64%,-dp/dtmax increased by 42.81% ±9.62%.There were no differences between these two groups.Conclusion Another receptor mechanism of CAR in heart failure model was probably blocked by β3AR.