Saha Cardiovascular Research Center, Lexington, KY 40536, USA.
Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands.
Biomolecules. 2022 Jun 13;12(6):825. doi: 10.3390/biom12060825.
In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice.
Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle ( = 5/group) or fludrocortisone ( = 15/group) into male ApoE mice fed a normal laboratory 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 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR mice fed Western diet reached statistical significance, compared to their vehicle.
Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies.
在一项旨在探索氟氢可的松引起高血压机制的实验中，我们意外地观察到给予氟氢可的松的小鼠出现主动脉瘤。本研究旨在探讨氟氢可的松是否会引起正常胆固醇和高胆固醇血症小鼠的主动脉病变。
雄性成年 C57BL/6J 小鼠给予载体（85%聚乙二醇 400（PEG-400）和 15%二甲基亚砜（DMSO）；n=5）或氟氢可的松（12mg/kg/天溶解于 85%PEG-400 和 15%DMSO；n=15）28 天。与给予载体的小鼠相比，氟氢可的松组小鼠的收缩压更高。氟氢可的松诱导 15 只小鼠中的 4 只出现主动脉病变，其中 3 只在升主动脉和主动脉弓区域出现病变，1 只在升主动脉和降主动脉胸段出现病变。腹部主动脉未见病变。随后，我们将载体（每组 n=5）或氟氢可的松（每组 n=15）分别输注至给予正常实验室饮食的 ApoE 小鼠或给予正常或西方饮食的 LDL 受体 小鼠。无论小鼠品系或饮食如何，氟氢可的松均使收缩压升高。在给予氟氢可的松的 ApoE 小鼠中，15 只中有 2 只出现升主动脉病变，但无腹部主动脉病变。在给予正常饮食的 LDL 受体 小鼠中，5 只出现升主动脉/弓部病变，1 只出现升主动脉、弓部和肾上主动脉区域的病变。在给予西方饮食的 LDL 受体 小鼠中，2 只死于降胸或腹主动脉破裂，13 只存活的小鼠中有 2 只出现升主动脉/弓部主动脉病变。主动脉病变包括出血、壁增厚或变薄或扩张。只有 LDLR 小鼠给予西方饮食的升主动脉直径与载体组相比有统计学意义。
氟氢可的松引起的主动脉病变与高胆固醇血症无关。从小鼠研究结果来看，正在服用或曾经服用氟氢可的松的人可能有更高的主动脉病变风险。
