Abstract 104: Cilnidipine Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms in Apolipoprotein E-deficient Mice via Its Anti-oxidative Stress Effect

Abstract

Objective: Chronic angiotensin II (AngII) infusion promotes development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Previous studies have shown that local inflammation and increased oxidative stress plays an important role on formation of AAAs. In addition, voltage-dependent N-type Ca 2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by AngII in mice. Last year, we reported that cilnidipine, an N/L-type calcium channel blocker, attenuated AngII-induced AAAs in apolipoprotein E deficient mice. The purposed of this study was to determine the mechanism of cilnidipine reducing AngII-induced AAAs Methods and Results: Male apolipoprotein E deficient mice (8-12 weeks old) were fed a normal laboratory diet. Mice were infused subcutaneously with either cilnidipine or vehicle by osmotic minipumps. Three days later, mice were also infused subcutaneously with either AngII (1,000 ng/kg/min, n = 14-16) or saline (n = 4) by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure. Cilnidipine decreased blood pressure in AngII-infused mice, but had not effect during saline infusion. Cilnidipine mildly restored plasma renin activity that were suppressed by AngII infusion. Cilnidipine mildly decreased plasma aldosterone concentrations that were increased by AngII infusion. Cilnidipine significantly reduced the incidence of AngII-induced AAAs (cilnidipine: 38 %, Vehicle: 88 %; P < 0.05). Elastica van Gieson staining demonstrated degeneration of elastic lamina by AngII was suppressed by cilnidipine administration. Immunohistochemical staining of CD68 revealed that cilnidipine administration attenuated accumulation of CD68 positive macrophage by AngII. In addition, cilnidipine reduced oxidative stress by AngII in 8-hydroxy-2’-deoxyguanosine and 4-Hydroxy-2-nonenal staining. Conclusion: Cilnidipine attenuated AngII-induced AAAs in male apolipoprotein E deficient mice by its anti-inflammation and anti-oxidative stress effect.