Abstract 560: Fludrocortisone Induces Aortic Pathologies In Mice

Abstract

Objective: Fludrocortisone, a corticosteroid, is used to treat adrenocortical insufficiency. In a previous study to determine associations between fludrocortisone-induced high blood pressure and angiotensin regulation, we observed aortic aneurysms in some fludrocortisone-infused mice. The purpose of this study was to investigate fludrocortisone-induced aortic pathologies in normocholesterolemic and hypercholesterolemic mice. Methods and Results: To determine whether fludrocortisone induces aortic aneurysms in normocholesterolemic mice, male C57BL/6J at 8 - 9 weeks of age were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); N=5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; N=15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compare to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending/arch region and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. To determine whether hypercholesterolemia augments fludrocortisone-induced aortic pathologies, we infused either vehicle (N=5/group) or fludrocortisone (N=15/group) into male ApoE -/- mice fed a normal diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 4 had ascending/arch aortic pathologies, 1 had pathologies in the ascending, arch and abdominal regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture, 4 had ascending/arch aortic pathologies, and 1 had pathologies in the ascending, arch and suprarenal aortic regions. Aortic pathologies were hemorrhage, wall thickening or thinning, or dilation. Given the low incidence, no quantification of aortic pathologies reached statistical significance. Conclusion: Fludrocortisone induces aortic pathologies with low incidence in both normo- and hypercholesterolemic mice.