Cardiac angiotensin-(1-7) in ischemic cardiomyopathy

Background - Accumulating evidence suggests that angiotensin-(1-7) (Ang-[1-7]) may play an important role in counteracting the pressor, proliferative, and profibrotic actions of angiotensin II in the heart. Thus, we evaluated whether Ang-(1-7) is expressed in the myocardium of normal rats and those in which myocardial infarction was produced 4 weeks beforehand. Methods and Results - The left coronary artery in 10-week-old Lewis rats was either ligated (n = 5) or exposed but not occluded in age-matched controls (sham; n = 5). Left ventricular end-diastolic pressures were significantly elevated 4 weeks after myocardial infarction (25 +/- 1 versus 5 +/- 1 mm Hg for sham; P < 0.001), whereas left ventricular systolic pressures were significantly reduced (ligated 86 +/- 4 versus sham 110 +/- 5 mm Hg; P < 0.01). Hemodynamic effects of coronary artery ligation were accompanied by significant cardiac hypertrophy (heart weight to body weight: ligated 4.3 +/- 0.1 versus sham 2.9 +/- 0.1 mg/g; P < 0.001). In both ligated and sham rats, Ang-(1-7) immunoreactivity was limited to cardiac myocytes and absent in interstitial cells and coronary vessels. Ang-(1-7) immunoreactivity was significantly augmented in ventricular tissue surrounding the infarct area in the heart of rats with myocardial infarction. Conclusions - Development of heart failure subsequent to coronary artery ligation leads to increased expression of Ang-(1-7), which was restricted to myocytes.