Lin Xinchun, Bernloehr Christian, Hildebrandt Tobias, Stadler Florian J, Doods Henri, Wu Dongmei
Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany.
Toxicol Appl Pharmacol. 2016 Aug 15;305:153-160. doi: 10.1016/j.taap.2016.06.005. Epub 2016 Jun 8.
The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats.
Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (±dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls.
The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor.
本研究的目的是评估新型激肽B1受体拮抗剂BI113823对心肌梗死后心脏重塑和心力衰竭的影响，并确定B1受体阻断是否会改变大鼠体内血管紧张素转换酶（ACE）抑制剂的心血管效应。
对Sprague Dawley大鼠进行左冠状动脉永久性闭塞。在心肌梗死后6周测定心血管功能。单独或联合使用B1受体拮抗剂（BI113823）或ACE抑制剂（赖诺普利）进行治疗，均显著降低了心脏重量与体重之比以及肺重量与体重之比，并改善了梗死后心脏功能，表现为心输出量增加、左心室压力上升最大速率（±dP/dtmax）、左心室射血分数、缩短分数增加，室壁运动改善，以及左心室舒张末期压力（LVEDP）升高的情况得到缓解。此外，与溶剂对照组相比，所有三个治疗组的心脏间质纤维化、胶原沉积、CD68阳性巨噬细胞、中性粒细胞以及促炎细胞因子产生（TNF-α和IL-1β）均显著减少。
本研究表明，新型激肽B1受体拮抗剂BI113823治疗可减轻心肌梗死后心脏重塑和心力衰竭，且不影响ACE抑制剂的心血管效应。
