Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors

Purpose: Pathologic remodeling of the extracellular matrix is a critical me chanism in the development and progression of abdominal aortic aneurysms (A AAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AkAs a re unknown. In this study we assessed the effect of ACE inhibitors in a rod ent model of aneurysm development. Methods: Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitor s (captopril [CP], lisinopril [LP], or enalapril [Er]), an angiotensin (AT) (1) receptor antagonist (losartan [LOS]), or water alone (9 rats in each gr oup). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (Delta A D) of more than 100%. The structural features of the aortic wall were exami ned by means of light microscopy. Results: Aneurysmal dilatation consistently developed within 14 days of ela stase perfusion in untreated rats, coinciding with the development of a tra nsmural inflammatory response and destruction of the elastic media (mean De lta AD, 223% +/- 28%). Ah three ACE inhibitors prevented AAA development (m ean Delta AD: 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 a neurysm-suppressing effects of ACE inhibitors were dissociated from their e ffects on systemic hemodynamics, and LOS had no significant effect on aneur ysm development compared with untreated controls (mean Delta AD, 186% +/- 1 9%). Conclusion: Treatment with ACE inhibitors suppresses the development of ela stase-induced AAAs in the rat. Although this is associated with the preserv ation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT(1) receptors. Further studies are needed to elucidate how ACE inhibitor s influence aortic wall matrix remodeling during aneurysmal degeneration.