抗钠钙交换体特异位点抗体对离体大鼠心脏功能和血管张力的影响及其与哇巴因、(±)Bay K8644作用的比较

Effects of site-specific antibody of Na+-Ca2 +exchanger on isolated rat heart functions /vascular tone and comparison with ouabain and( ± ) Bay K8644

目的:比较抗钠钙交换体(NCX)特异位点(α-1重复序列124HNFTAGDLGPSTIVGSAAFNMF145)抗体、传统强心药哇巴因以及L型Ca2+通道激动剂(±)Bay K8644对离体大鼠心脏和血管功能的影响,以探求新的强心作用靶点。方法:选用成年大鼠,体重250～300 g,快速分离心脏和胸主动脉,利用Langendorff离体心脏灌流装置和血管环张力测定系统观察10 nmol/L、20 nmol/L和40 nmol/L抗NCX特异位点抗体以及哇巴因(0.5mmol/L)、(±)Bay K8644(0.1 mmol/L)对心脏血流动力学指标左室发展压、左心室内压上升/下降最大速率(±dp/dt max)、冠脉阻力以及胸主动脉环张力的影响。结果:10 nmol/L、20 nmol/L和40nmol/L抗NCX特异位点抗体剂量依赖性地使大鼠离体心脏左室发展压、+dp/dt max和-dp/dt max增加,表明心脏收缩和舒张效率均增强。给药过程中均没有发生心律失常。哇巴因(0.5 mmol/L)和(±)Bay K8644(0.1 mmol/L)对正常离体灌流大鼠心脏左室发展压及+dp/dt max也有增强作用,作用强度与抗NCX特异位点抗体(40 nmol/L)的作用相当,但(±)Bay K8644(0.1 mmol/L)对-dp/dt max无明显影响,哇巴因(0.5 mmol/L)则有使-dp/dt max下降的趋势。哇巴因(0.5 mmol/L)在给药5 min后,多数离体心脏出现≥5 beats/min的早博,(±)Bay K8644(0.1 mmol/L)给药过程中离体大鼠心脏没有出现心律失常。结论:抗NCX特异位点抗体可以同时增强离体灌流大鼠心脏的收缩和舒张活动,并且不增加心律失常的发生率,同时对灌流心脏冠脉阻力以及离体大鼠的胸主动脉环张力也没有显著影响。

AIM：To investigate the effects of site-specific （α-1 repeat： 124HNFTAGDLGPSTIVGSAAFNMF145） antibody of Na＋-Ca2＋ exchanger （NCX） on the isolated rat heart functions and vascular tone and to compare them with the effects of Na＋-K＋ pump inhibitor ouabain and L-type Ca2＋ channel agonist （±）Bay K8644. METHODS：The heart and thoracic aorta were rapidly isolated from the adult rats weighing 250～300 g. The hemodynamic indexes including left ventricular developed pressure, maximal rate of rise/decline of left ventricular pressure （±dp/dtmax） and coronary resistance were observed by Langendorff isolated heart perfusion system. The rings of thoracic aorta were mounted into the organ baths and the vascular tone was determined. RESULTS：At concentrations of 10, 20 and 40 nmol/L, the site-specific antibody of NCX enhanced the cardiac functions in a dose-dependent manner during the perfusion period with no arrhythmia. At the same time, it did not increase the coronary resistance. The antibody had no effect on the vascular tone of isolated thoracic aorta ring at the same concentrations. Ouabain at concnentration of 0.5 mmol/L and （±）Bay K8644 at concentration of 01 mmol/L had similar effects with the site-specific antibody of NCX at concentration of 40 nmol/L on left ventricular developed pressure and ＋dp/dtmax of isolated rat hearts during perfusion, but （±）Bay K8644 （01 mmol/L） didn’t have significant effect on -dp/dtmax. Ouabain （0.5 mmol/L） even reduced -dp/dtmax as compared with the control. After administration of ouabain （0.5 mmol/L） for 5 min, most isolated hearts appeared premature pulse more than 5 beats/min. （±）Bay K8644 （0.1 mmol/L） did not induce arrhythmia during all the time of exposure. CONCLUSION： The site-specific （α-1 repeat： 124HNFTAGDLGPSTIVGSAAFNMF145） antibody of NCX enhances both systolic and diastolic functions of isolated rat hearts without arrhythmia. Meanwhile, this antibody doesn’t increase coronary resistance during perfusion and vascular tone in isolated thoracic aorta rings.