imidapril and Aortic-Aneurysm--Abdominal

To clarify the matrix metalloproteinase (MMP)-9 inhibitory effect of an angiotensin-converting enzyme (ACE) inhibitor in vivo, we evaluated the effect of an ACE inhibitor against elastase-induced abdominal aortic aneurysm (AAA) progression in mice. Molecular models showed that imidapril bound directly to the mouse MMP-9 active center. An active form of imidapril, imidaprilat, dose-dependently inhibited MMP-9 activity in the extract from elastase-induced AAA in wild-type mice. Imidapril (10 mg/kg per day) was administered to wild-type or angiotensin II type 1 (AT1) receptor knockout mice. Blood pressure was significantly lower in AT1 receptor-knockout mice than in wild-type mice, but imidapril did not affect blood pressure in AT1 receptor-knockout mice. The aortic diameter was significantly expanded after elastase application, but the expansion was significantly lower in AT1 receptor-knockout mice than in wild-type mice. In AT1 receptor-knockout mice, the aortic expansion was further attenuated by imidapril. MMP-9 activity in aorta was significantly augmented after elastase application. The MMP-9 activity was significantly lower in AT1 receptor-knockout mice than in wild-type mice, and it was further attenuated by imidapril. In conclusion, MMP-9 inhibition by imidapril might contribute to the attenuation of AAA progression in AT1 receptor-knockout mice.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Aortic Aneurysm, Abdominal; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Gene Knockout Techniques; Imidazolidines; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Pancreatic Elastase; Receptor, Angiotensin, Type 1; Ultrasonography