Fludrocortisone Induces Aortic Pathologies in Mice

Dien Ye, Congqing Wu, Hui Chen, Ching Ling Liang, Deborah A. Howatt, Michael K. Franklin, Jessica J. Moorleghen, Samuel C. Tyagi, Estrellita Uijl, A. H. Jan Danser, Hisashi Sawada, Alan Daugherty, Hong S. Lu*

*Corresponding author for this work

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Abstract

Background and Objective: 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 fludrocor-tisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice 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, 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 (n = 5/group) or fludrocortisone (n = 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 su-prarenal 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 dila-tion. Only ascending aortic diameter in LDLR ‐/‐ mice fed Western diet reached statistical signifi-cance, compared to their vehicle. Conclusion: 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.

Original languageEnglish
Article number825
JournalBiomolecules
Volume12
Issue number6
DOIs
Publication statusPublished - 13 Jun 2022

Bibliographical note

Funding Information:
Funding: The authors’ research work is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award numbers R00HL145117, R01HL139748, and R35HL155649. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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