Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats.
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.
Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
Xinchun
X
Lin
Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany.
Christian
C
Bernloehr
Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany.
Tobias
T
Hildebrandt
Shenzhen Engineering Laboratory for Advanced Technology of Ceramics, Shenzhen 518060, PR China. Electronic address: fjstadler@szu.edu.cn.
Florian J
FJ
Stadler
Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany.
Henri
H
Doods
Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140, USA; Department of BIN Convergence Technology, Chonbuk National University, South Korea. Electronic address: dongmeiwu@bellsouth.net.
Dongmei
D
Wu
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D065169:Bradykinin B1 Receptor Antagonists / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D017706:Lisinopril
Angiotensin 1 converting enzyme; Cardiac function; Cardiac remodeling; Hemodynamics; Kinin B1 receptor