lisinopril and Aortic-Aneurysm--Abdominal

Angiotensin (Ang) II-induced abdominal aortic aneurysm (AAA) in apoE-deficient mice has been used as a model of human AAA, but it has been unclear why the progression of AAA continues after stopping the Ang II infusion. The involvement of vascular Ang II-forming enzymes in the progression of AAA was studied.. ApoE-deficient mice were infused with Ang II (1,000 ng/kg/min) for 4 weeks and evaluated until 20 weeks after the Ang II infusion. Just after and 20 weeks after stopping the Ang II infusion, the degree of AAA, as well as the ACE and chymase activities, was evaluated. An Ang II receptor blocker (candesartan, 30 mg/kg/day) and an angiotensin-converting enzyme (ACE) inhibitor (lisinopril, 60 mg/kg/day) were given for 20 weeks after stopping the Ang II infusion.. The aortic diameter expanded just after stopping the Ang II infusion and progressed for a further 20 weeks after the infusion was stopped. Just after stopping the infusion, aortic ACE and chymase activities were significantly increased, but only the increase in chymase activity continued until 20 weeks after the infusion was stopped. Candesartan and lisinopril significantly attenuated aortic diameter expansion.. The increases in vascular Ang II-forming activities were involved in the progression of AAA after stopping the Ang II infusion.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Aortic Aneurysm, Abdominal; Apolipoproteins E; Benzimidazoles; Biphenyl Compounds; Chymases; Disease Progression; Lisinopril; Mice; Mice, Knockout; Peptidyl-Dipeptidase A; Tetrazoles

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.. 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.. 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%).. 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.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Pressure; Captopril; Enalapril; Lisinopril; Losartan; Male; Pancreatic Elastase; Rats; Rats, Wistar