Effects of Angiotensin Receptor Blocker and Calcium Channel Blocker on Experimental Abdominal Aortic Aneurysms in a Hamster Model

Abstract

Summary: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.Key words abdominal aortic aneurysm, matrix metalloproteinase-9, matrix metalloproteinase-2, angiotensin II receptor antagonist, olmesartan medoxomil

Statin Therapy Reduces Growth of Abdominal Aortic Aneurysms

“…However, because the nonstatin users had the greater use of CCB (Table 2), this variable did not contribute to our primary finding of the protective effect of statins on aneurysm growth. The potential protective effect of CCB is consistent with animal studies showing inhibition in progression of experimental AAA by CCB, in part through suppression of MMP activity 55,56 ; however, the protective role of CCB has not been found in human AAAs. 57 This study has several methodological limitations.…”

Nifedipine attenuation of abdominal aortic aneurysm in hypertensive and non-hypertensive mice: Mechanisms and implications

“…It has been reported that, in a well characterized murine model of AAA, namely angiotensin II (Ang II) infused apoE null mice, AAA formation is independent of blood pressure elevation [2–4], and some potential treatments against AAA usually do not alter blood pressure in animal models [5]. However, these data do not completely rule out a potential link between blood pressure and AAA in general or in different animal models.…”

Renin-angiotensin system blockade does not attenuate abdominal aortic aneurysm growth, rupture rate, or perioperative mortality after elective repair

“…3,4 Furthermore, studies employing the use of ACEis and ARBs have demonstrated the complete attenuation or regression of AAAs in both Ang II-induced and Ang II-independent mouse models of AAA. [5][6][7][8][9][10][11] However, these effects may not be transferable to human patients.…”