Cardiac Myocyte Necrosis Induced by Angiotensin II

Although the role of angiotensin II (Ang II) in the pathogenesis and progression of the failing heart is uncertain, previous reports have suggested that myocyte injury may be a component in this process. In this study, we investigated this possibility in more detail. Cardiotoxic effects of nonacutely hypertensive doses of Ang II were examined in 90 rats, including those receiving an angiotensin infusion (200 ng/min i.p.) and those with renovascular hypertension, where endogenous stimulation of Ang II occurred. Myocyte injury and wound healing resulting from these treatments were evaluated by 1) immunofluorescence after in vivo monoclonal antibody labeling of myosin to detect abnormal sarcolemmal permeability, 2) [H]thymidine incorporation into DNA, to detect fibroblast proliferation, and 3) light microscopic evidence of myocytolysis and subsequent scar formation. We found that exogenous Ang II produced multifocal antimyosin labeling of cardiac myocytes and myocytolysis, which were maximal on days 1–2 of the infusion. Subsequently, DNA synthesis rates were increased, with fibroblast proliferation reaching peak levels on day 2 (Ang II-treated rats, 90.0±18.6 cpm/μg DNA; control rats, 11.4±2.3 cpm/μg DNA; p