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 underlie 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 AT1 receptor subtype. Also, vascular outgrowth is functionally diminished, an effect that seems to depend on AT2 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 AT1 antagonists are appropriate early after MI. AT2 antagonists administered at that time can inhibit the cardiac vascularization response and cause a further decrease in level of cardiac function.
Smits
J F
JF
Department of Pharmacology, Cardiovascular Research Institute Maastricht, The Netherlands.
Passier
R C
RC
Nelissen-Vrancken
H J
HJ
Cleutjens
J P
JP
Kuizinga
M C
MC
Daemen
M J
MJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004719:Endomyocardial Fibrosis / Q000473:pathology; D006333:Heart Failure / Q000473:pathology*; D006801:Humans; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen