Does ACE inhibition limit structural changes in the heart following myocardial infarction?

A recent series of experiments in our laboratory were designed to elucidate the cellular changes that underline the cardiac remodelling response following myocardial infarction (MI) in the rat as well as the potential role of the renin-angiotensin system (RAS) in this response. Inhibition of the RAS interferes with cardiomyocyte hypertrophy, interstitial cell DNA synthesis, and collagen deposition, these effects are mediated through the angiotensin II AT(1) receptor subtype. Also, vascular outgrowth is functionally diminished, an effect that seems to depend on AT(2) receptor activation. The intracardiac RAS may be involved in the wound healing response in the infarct area. However, we found no evidence for activation of the RAS in the remnant myocardium, which suggests that myocyte hypertrophy and interstitial fibrosis depend on activation of the systemic RAS. During the first weeks following MI, therapy of choice should thus inhibit the systemic RAS while allowing the wound-healing response of the intracardiac RAS, i.e. selective AT(1) antagonists are appropriate early, after MI. AT(2) antagonists administered at that time can inhibit the cardiac vascularization response and cause a further decrease in level of cardiac function.