Angiotensin II Type 2 Receptor Stimulation

• DOI: 10.1161/circulationaha.108.784868
• Publication Date: 2008-11-25T02:37:51Z
• Authors: Elena Kaschina; Aleksandra Grzesiak; Jun Li; Anna Foryst-Ludwig; Melanie Timm; Franziska Rompe; Manuela Sommerfeld; U. Rudolf Kemnitz; Caterina Curato; Pawel Namsolleck; Carsten Tschöpe; Anders Hallberg; Mathias Alterman; Thomas Hucko; Ingo Paetsch; Thore Dietrich; Bernhard Schnacke...; Kristof Graf; Björn Dahlöf; Ulrich Kintscher; Thomas Unger; U. Muscha Steckel...
• Keywords: Diagnostic Imaging; Inflammation; Dose-Response Relationship, Drug; Hemodynamics; Myocardial Infarction; Apoptosis; Receptor, Angiotensin, Type 2; Rats; 3. Good health; Renin-Angiotensin System; 03 medical and health sciences; 0302 clinical medicine; Animals; Rats, Wistar

Background— This study is the first to examine effect of direct angiotensin II type 2 (AT ) receptor stimulation on postinfarct cardiac function with use novel nonpeptide AT agonist compound 21 (C21). Methods and Results— Myocardial infarction (MI) was induced in Wistar rats by permanent ligation left coronary artery. Treatment C21 (0.01, 0.03, 0.3 mg/kg per day IP) started 24 hours after MI continued until euthanasia (7 days MI). Infarct size assessed magnetic resonance imaging, hemodynamic measurements were performed via transthoracic Doppler echocardiography intracardiac Millar catheter. Cardiac tissues analyzed for inflammation apoptosis markers immunoblotting real-time reverse transcription polymerase chain reaction. significantly improved systolic diastolic ventricular function. Scar smallest C21-treated rats. In regard underlying mechanisms, diminished MI-induced Fas-ligand caspase-3 expression peri-infarct zone, indicating an antiapoptotic effect. Phosphorylation p44/42 p38 mitogen-activated protein kinases, both involved regulation cell survival, strongly reduced but almost completely rescued treatment. Furthermore, decreased serum monocyte chemoattractant protein-1 myeloperoxidase as well interleukin-6, interleukin-1β, interleukin-2 expression, suggesting antiinflammatory Conclusions— Direct may be a therapeutic approach improve post-MI mechanisms.