Mechanisms of combined treatment with celiprolol and candesartan for ventricular remodeling in experimental heart failure.
Mechanisms of combined treatment with celiprolol and candesartan for ventricular remodeling in experimental heart failure.
复制标题
塞利洛尔和坎地沙坦联合治疗实验性心力衰竭心室重构的机制。
DOI：
10.1253/circj.69.596
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Y. Kitaura
中科院分区：
文献类型：
--
作者：
Tatsuhiko Mori;Tetsuya Hayashi;K. Sohmiya;Nobuaki Okuda;H. Shimomura;M. Ohkita;Y. Matsumura;M. Yoshiyama;J. Yoshikawa;Y. Kitaura
背景
据报道，β-肾上腺素能受体阻滞剂和血管紧张素II受体阻滞剂均可改善心力衰竭患者的预后，但这些药物联合治疗的疗效尚未完全阐明。塞利洛尔是一种β 1选择性肾上腺素受体拮抗剂，具有部分β 2激动剂特性，其治疗心力衰竭的疗效仍有争议。我们研究了塞利洛尔或坎地沙坦，血管紧张素II受体阻滞剂和他们的联合治疗对异丙肾上腺素（ISO）诱导的心力衰竭的心脏保护作用和机制。
方法和结果
ISO 300 mg/kg注射于大鼠，造成心力衰竭。注射后两个月，将注射ISO的大鼠分成4组（每组8只大鼠），并如下处理4周：（a）赋形剂;（B）塞利洛尔10 mg/kg/天（BB）;（c）坎地沙坦0.2 mg/kg/天（AR B）;和（d）它们的组合BB+ AR B。ISO显著升高左心室（LV）舒张末期压，降低峰值负dP/dt和LV射血分数。BB和ARB相似地改善了ISO引起的心功能不全，但BB+ARB比单独治疗更有效。另外，ARB保留了LV心肌的组织结构。相比之下，BB改善钙处理，如SERCA 2与受磷蛋白的比率增加所示，尽管对组织学几乎没有影响。
结论
塞利洛尔和坎地沙坦在该心力衰竭模型中均显示出心脏保护作用。联合治疗心力衰竭的潜在用途可能通过塞利洛尔和坎地沙坦的不同心脏保护机制产生协同效应。
BACKGROUND
Both beta-adrenergic blockers and angiotensin-II receptor blockers were reported to improve the prognosis of patients with heart failure, but the efficacy of combination therapy with these agents has not been fully elucidated. Also the efficacy of celiprolol, a beta1-selective adrenoceptor antagonist with partial beta2-agonist properties, for heart failure treatment is still controversial. We examined the cardioprotective effects and mechanisms of the therapy with celiprolol or candesartan, an angiotensin-II receptor blockers and their combination in heart failure induced by isoproterenol (ISO).
METHODS AND RESULTS
ISO 300 mg/kg was injected in rats to produce heart failure. Two months after the injection, the ISO-injected rats were divided into 4 groups (8 rats each) and treated for 4 weeks as follows: (a) vehicle; (b) celiprolol 10 mg/kg per day (BB); (c) candesartan 0.2 mg/kg per day (ARB); and (d) their combination BB+ARB. ISO significantly elevated left ventricular (LV) end-diastolic pressure, decreased peak-negative dP/dt and LV ejection fraction. BB and ARB similarly ameliorated cardiac dysfunction due to ISO, but BB+ARB were more potent than the individual therapies. Separately, ARB preserved the histological structure in LV myocardium. In contrast, BB ameliorated calcium handling, as shown by the increased ratio of SERCA2 to phospholamban protein, despite having little effect on the histology.
CONCLUSION
Both celiprolol and candesartan showed cardioprotective effects in this heart failure model. The potential use of the combination treatment in heart failure might result in a synergistic effect through the different cardioprotective mechanisms of celiprolol and candesartan.
左心室球形度对弥漫性异丙肾上腺素诱导心肌坏死大鼠心室功能障碍演变的影响。
DOI：
10.1016/s1071-9164(98)90507-3
发表时间：
1998
期刊：
Journal of cardiac failure.
影响因子：
--
作者：
Teerlink,JR;Pfeffer,JM;Pfeffer,MA
通讯作者：
Pfeffer,MA
非衰竭和衰竭人类心肌中 Ca(2 ) 转运 ATP 酶、受磷蛋白和钙螯合蛋白水平。
影响因子：
37.8
作者：
Movsesian,MA;Karimi,M;Green,K;Jones,LR
通讯作者：
Jones,LR
冠状动脉结扎或注射异丙肾上腺素诱导的心肌坏死动物模型中的诱导型一氧化氮合酶和肿瘤坏死因子。
DOI：
10.1016/s1071-9164(99)90008-8
发表时间：
1999
期刊：
Journal of cardiac failure.
影响因子：
--
作者：
Grosjean,SA;Arstall,MA;Mitchell,RN;Klappacher,GW;Kelly,RA;Pfeffer,MA;Pfeffer,JM
通讯作者：
Pfeffer,JM