Involvement of Vascular Angiotensin II-Forming Enzymes in the Progression of Aortic Abdominal Aneurysms in Angiotensin II- Infused ApoE-Deficient Mice

• Published in: Journal of Atherosclerosis and Thrombosis 2009, Vol.16(3), pp.164-171
• Main Authors: Inoue, Nao, Muramatsu, Michiko, Jin, Denan, Takai, Shinji, Hayashi, Tetsuya, Katayama, Hiroshi, Kitaura, Yasushi, Tamai, Hiroshi, Miyazaki, Mizuo
• Format: Article
• Language: English
• Subjects: Aneurysm; Angiotensin II; Angiotensin II - toxicity; Angiotensin II Type 1 Receptor Blockers; Angiotensin-converting enzyme; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta - enzymology; Aortic Aneurysm, Abdominal - chemically induced; Aortic Aneurysm, Abdominal - pathology; Apolipoproteins E - deficiency; Benzimidazoles - pharmacology; Chymase; Chymases - physiology; Disease Progression; Lisinopril - pharmacology; Mice; Mice, Knockout; Peptidyl-Dipeptidase A - physiology; Tetrazoles - pharmacology
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.E611

Aim: 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. Methods: 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. Results: 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. Conclusion: The increases in vascular Ang II-forming activities were involved in the progression of AAA after stopping the Ang II infusion.