Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors.
OBJECTIVE
Pathologic remodeling of the extracellular matrix is a critical mechanism in the development and progression of abdominal aortic aneurysms (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AAAs are unknown. In this study we assessed the effect of ACE inhibitors in a rodent model of aneurysm development.


METHODS
Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [EP]), an angiotensin (AT)1 receptor antagonist (losartan [LOS]), or water alone (9 rats in each group). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (DeltaAD) of more than 100%. The structural features of the aortic wall were examined by means of light microscopy.


RESULTS
Aneurysmal dilatation consistently developed within 14 days of elastase perfusion in untreated rats, coinciding with the development of a transmural inflammatory response and destruction of the elastic media (mean DeltaAD, 223% +/- 28%). All three ACE inhibitors prevented AAA development (mean DeltaAD: CP, 67% +/- 4%; LP, 18% +/- 12%; and EP, 14% +/- 3%; each P <.05 vs controls). ACE inhibitors also attenuated the degradation of medial elastin without diminishing the inflammatory response. Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated from their effects on systemic hemodynamics, and LOS had no significant effect on aneurysm development compared with untreated controls (mean DeltaAD, 186% +/- 19%).


CONCLUSIONS
Treatment with ACE inhibitors suppresses the development of elastase-induced AAAs in the rat. Although this is associated with the preservation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT1 receptors. Further studies are needed to elucidate how ACE inhibitors influence aortic wall matrix remodeling during aneurysmal degeneration.
Liao
S
S
Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St Louis, MO, USA.
Miralles
M
M
Kelley
B J
BJ
Curci
J A
JA
Borhani
M
M
Thompson
R W
RW
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D017706:Lisinopril / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010196:Pancreatic Elastase; D051381:Rats; D017208:Rats, Wistar
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril; D017706:Lisinopril; D010196:Pancreatic Elastase; D019808:Losartan