Effects of angiotensin receptor blocker and calcium channel blocker on experimental abdominal aortic aneurysms in a hamster model

Abstract

Remodeling in the abdominal aortic wall results in abdominal aortic aneurysm (AAA) formation. Many patients with AAA are prescribed antihypertensive drugs. However, the effects of antihypertensive drugs other than their effects on blood pressure control are rarely reported. In this study, we investigated the effects of these drugs on changes in the levels of matrix metalloproteinases (MMPs) and on AAA formation. Experimental AAAs were created in a hamster model by wrapping the abdominal aorta with elastase gauze. Olmesartan medoxomil (angiotensin II receptor antagonist) or azelnidipine (calcium channel antagonist) was administered to the hamsters and then we evaluated the aortic diameter, performed histological analysis, and analyzed the production of MMP-2 and MMP-9 by gelatin zymography. The expansion rate of the aortic diameter was smaller in both treatment groups than in the control group. Elastica van Gieson (EVG) staining showed structural preservation of elastin lamellae in both treatment groups. The active MMP-9 level decreased in both the olmesartan group and the azelnidipine group. Reducing MMP-9 production is important for suppression of AAA formation. Both olmesartan medoxomil and azelnidipine decreased MMP-9 activity, which suppressed degradation of the MMPs and inhibited AAA formation. There are different cascades that determine the production of MMP-9.