Exercise Training Reduces AngII and Increases Ang‐(1‐7) Concentration in Cardiac Muscle of CHF Rats

Abstract

ACE‐AngII axis of the renin angiotensin‐system is increased in the heart of chronic heart failure (CHF) and contributes to its pathophysiology. Recent studies show that ACE2‐Ang‐(1‐7) counteracts the ACE‐AngII effects. However, the cardiac balance between ACE‐AngII/ACE2‐Ang‐(1‐7) in CHF remains unknown. We studied: 1) The cardiac ACE‐AngII/ACE2‐Ang‐(1‐7) balance in CHF; and 2) The effects of exercise training (ExT, treadmill running, 60min/d, 5 d/wk, 60% VO2max for 8wk) on ACE‐AngII/ACE2‐Ang‐(1‐7) balance in the heart of CHF rats. Male Wistar rats underwent coronary artery ligation for CHF induction or sham surgery (C). Four weeks later, they were divided into four groups: 1) C (untrained), 2) C+ExT, 3) CHF and 4) CHF+ExT. ExT. CHF or ExT did not change cardiac ACE activity (fluorimetry, uF/min/mg). In contrast, CHF increased cardiac AngII concentration (HPLC, 139.1±22.6 and 96.8±8.1 pmol/mg) and ExT reduced it (70.4±9.7 pmol/mg, P=0.01). Unexpectedly, CHF provoked an increase in ACE2 activity. ExT increased ACE2 activity, even further in the CHF+ExT rats. CHF caused no changes in Ang‐(1‐7). ExT increased cardiac Ang‐(1‐7) concentration in both C and CHF rats, which resulted in an augmented Ang‐(1‐7)/AngII ratio. We conclude that CHF provokes an imbalance in cardiac ACE‐AngII/ACE2‐Ang‐(1‐7) toward ACE‐AngII axis. ExT counteracts this imbalance by increasing cardiac ACE2‐Ang‐(1‐7) axis. Sponsored by FAPESP, CNPq and CAPES.