• Research Initiatives Conference
• Coding & Reimbursement Course
• Vascular Annual Meeting^®
• CME Mission
• VESAP®
• Calendar of Pages

Home > Medical Professionals > Research Initiatives Conference > Poster Abstracts Accepted > NADPH Oxidase Inhibition Suppresses

NADPH Oxidase Inhibition Suppresses Aortic Aneurysm Formation

Jason N MacTaggart, Jason M Johanning, Wanfen Xiong, Iraklis I Pipinos, Rebecca Knispel, B. Timothy Baxter
University of Nebraska Medical Center, Omaha, NE

Objective: Oxidative stress plays a role in abdominal aortic aneurysm (AAA) formation. Nitric oxide in combination with superoxide forms peroxynitrite which is present in both human and animal AAAs. The source of nitric oxide has been investigated but the source of superoxide is unknown. NADPH oxidase and xanthine oxidase are the likely enzymes involved in superoxide production. Our study examined the ability of selective blockade of these two pathways to inhibit aneurysm formation in a mouse model of AAA.
Methods: Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 8 weeks later, groups of C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor) or oxypurinol (xanthine oxidase inhibitor). Control mice were given water. AAAs were induced in all animals by periaortic application of calcium chloride. Aortic diameter was measured with video microscopy at aneurysm induction and harvest. The mean diameter and diameter change of each treatment group were compared with concurrent controls using the Mann-Whitney test.
Results: NADPH oxidase inhibition by apocynin blocked aneurysm formation (*P=0.001), while xanthine oxidase inhibition with oxypurinol did not (**P=N.S.).

	Pre	Post	% Increase
Apocynin n=7	540±9µm	574±11µm*	6%±3%
Apocynin concurrent control n=6	529±15µm	813±12µm*	53%±4%
Oxypurinol n=7	527±12µm	712±36µm**	35%±7%
Oxypurinol concurrent control n=7	525±14µm	717±45µm**	37%±9%

Conclusion: Treatment of mice with apocynin, an NADPH oxidase inhibitor, suppresses aneurysm formation in the calcium chloride model of AAA, while treatment with oxypurinol, a xanthine oxidase inhibitor, has no effect. This study suggests that the NADPH oxidase pathway makes an important contribution to the reactive oxygen species involved in AAA development.