Abstract 276: Nicotine Infusion Fails to Induce Abdominal Aortic Aneurysmsin LDL Receptor Deficient Mice
Background and Objective Smoking is a major risk factor for the development of abdominal aortic aneurysms (AAA). Although there are a large number of chemical constituents of smoke, recent evidence demonstrated that nicotine infusion to apoE -/- mice induces AAA formation. These nicotine-induced AAAs share many characteristics to those formed during infusion of angiotensin II (AngII). The purpose of this study was to contrast the susceptibility of AAAs induced by nicotine versus AngII in LDL receptor -/- mice.
Methods and Results Ten-week-old male LDL receptor -/- mice were fed a saturated-fat supplemented diet for 7 weeks. One week after the initiation of the fat-enriched diet feeding, mice were randomized into 3 groups: saline infusion (N = 5), AngII (1 μg/kg/min; N = 5) infusion, and nicotine (5 μg/kg/min; N = 10) infusion, respectively, for 6 weeks. Infusions were performed using mini-osmotic pumps implanted subcutaneously. Cotinine is the major metabolite of nicotine. Plasma concentrations of cotinine were undetectable in saline and AngII-infused mice, but were at detectable levels (87 ± 28 ng/ml) in nicotine-infused mice. Despite measurable plasma concentrations of cotinine, nicotine infusion had no effect on body weight, systolic blood pressure, plasma total cholesterol concentrations, and lipoprotein-cholesterol distribution. Also, we were unable to discern any nicotine-induced changes in the lumen diameter of suprarenal aortas in live mice using high frequency ultrasound or maximum width of suprarenal aortas (0.94 ± 0.02 mm) measured ex vivo after termination. In contrast, AngII infusion promoted aortic rupture (N = 2/5 = 40%) and profoundly increased maximal width of suprarenal aortas (1.83 ± 0.20 mm) compared to mice infused with saline (0.91 ± 0.04 mm).
Conclusion In contrast to AngII, infusion of nicotine does not induce AAA formation in LDL receptor -/- mice.
- © 2013 by American Heart Association, Inc.