195 Angiotensin-(1-9) Reduces Cardiac Dysfunction in a Model of Angiotensin II-Induced Hypertensive Heart Disease

Angiotensin II (AngII) is involved in the pathophysiology of cardiovascular diseases including hypertension, myocardial infarction and heart failure. The counter-regulatory axis of the renin angiotensin system is centred on angiotensin-converting-enzyme 2 generating angiotensin-(1-7) which opposes the pathological actions of AngII in the heart. We recently showed that angiotensin-(1-9) [Ang-(1-9)] is part of the counter-regulatory axis which acts on the angiotensin type 2 receptor to inhibit AngII-induced cardiomyocyte hypertrophy in vitro and the development of cardiac fibrosis and hypertrophy in the stroke prone spontaneously hypertensive rat. 1 Here, we characterised chronic effects of AngII infusion on cardiac function in mice and assessed whether Ang-(1-9) can reverse AngII-induced cardiac pathology. In study 1, C57BL/6J mice were infused with H 2 O (control), 24 μg/kg/hr or 48 μg/kg/hr AngII for 6 weeks via osmotic minipumps. A separate group was infused with Ang-(1-9) (48 μg/kg/hr) alone to assess direct effects on cardiac function. In study 2, mice were infused with H 2 O or 48 μg/kg/hr AngII for 2 weeks, minipumps were replaced and mice received either H 2 O, AngII or AngII with Ang-(1-9) for a further 2 weeks. Cardiac function was measured by echocardiography and histological staining for cardiac fibrosis and cardiomyocyte hypertrophy performed. After 6 weeks AngII infusion, fractional shortening (FS) was significantly decreased with either dose [control 45.5 ± 1.8%; AngII (24 μg) 32.3 ± 1.8%; AngII (48μg) 36.6 ± 4.2%; p These results demonstrate that Ang-(1-9) can limit AngII-induced cardiac dysfunction and therefore has therapeutic potential in a range of cardiovascular diseases. Reference Flores-Munoz M et al . Hypertension. 2012;59(2):300-7