The bradykinin B1 receptor contributes to the cardioprotective effects of AT1 blockade after experimental myocardial infarction

• Published in: Cardiovascular research Vol. 61; no. 3; pp. 559 - 569
• Main Authors: TSCHÖPE, Carsten, SPILLMANN, Frank, SCHULTHEISS, Heinz-Peter, WALTHER, Thomas, ALTMANN, Christine, KOCH, Matthias, WESTERMANN, Dirk, DHAYAT, Nasser, DHAYAT, Sameer, BASCANDS, Jean-Loup, GERA, Lajos, HOFFMANN, Sigrid
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.02.2004
• Subjects: Angiotensin II Type 1 Receptor Blockers; Animals; Biological and medical sciences; Biphenyl Compounds - therapeutic use; Cardiology. Vascular system; Coronary heart disease; Gene Expression; Heart; Male; Medical sciences; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocarditis. Cardiomyopathies; Myocardium - chemistry; Myocardium - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1 - analysis; Receptor, Bradykinin B1 - analysis; Receptor, Bradykinin B1 - genetics; Receptor, Bradykinin B1 - metabolism; RNA, Messenger - analysis; RNA, Messenger - metabolism; Tetrazoles - therapeutic use; Myocardial infarction; Vasodilator agent; Cardiovascular disease; Myocardial disease; Neuropeptide; Coronary heart disease; Phlebology; Signal transduction; Renin angiotensin system; Bradykinin; Infarction; Circulatory system; Hemodynamics; Cardiology; Biological receptor
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2003.10.018

To investigate the role of the bradykinin B1 receptor (B1R) on the angiotensin receptor AT1 blockade-dependent cardioprotective effects, we studied the B1R regulation in wild-type rats treated with the AT1 antagonist, irbesartan (IRB), and also in transgenic rats with cardiac overexpression of the human AT1 (TGR-alphaMHCAT1) after induction of myocardial infarction (MI). In addition, we treated wild-type rats with IRB and/or the B1R antagonist, B9958, and determined the left ventricular (LV) function. Untreated, IRB (50 mg/kg/day/p.o.), B9958 (0.1 mg/kg/48 h/s.c.), and IRB/B9958-treated Sprague-Dawley rats were submitted to a permanent occlusion of the left descending coronary artery. Six days and three weeks after induction of MI, the LV function was characterized by using a Millar-tip catheter. Myocardial AT1- and B1-mRNA expression were analyzed by RNase-protection assays, B1R protein density by immunohistochemistry. At both time points, LV function had improved by almost 50% after treatment with IRB but remained unchanged in TGR-alphaMHCAT1 after induction of MI compared to their untreated controls. The beneficial effect of IRB was reversed by co-treatment with B9958. The B1R antagonist treatment alone had no effect. A cross-talk between AT1 and B1R was also indicated by an up-regulation of B1R after treatment with IRB on protein and RNA level, while AT1 overexpression reduced B1R expression after induction of MI. These results indicate that the mechanisms of B1R regulation are influenced by the AT1 receptor. Thus, we are able to demonstrate for the first time that the B1R contributes to the cardio-beneficial effects of AT1 blockade.