Published Online
on September 29, 2003

A more recent version of this article appeared on October 28, 2003

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Submitted on December 31, 2002
Revised on June 23, 2003
Accepted on June 24, 2003

Cardiac Angiotensin-(1-7) in Ischemic Cardiomyopathy

David B. Averill PhD^*, Yuichiro Ishiyama MD, Mark C. Chappell PhD, and Carlos M. Ferrario MD

From The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC.

^* To whom correspondence should be addressed. E-mail: daverill{at}wfubmc.edu.

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.

Key words: heart failure • angiotensin • myocardial infarction • cardiomyopathy

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