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Fludrocortisone Induces Aortic Pathologies in Mice

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 fludrocortisone induces aortic patholo...

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Autores principales: Ye, Dien, Wu, Congqing, Chen, Hui, Liang, Ching-Ling, Howatt, Deborah A., Franklin, Michael K., Moorleghen, Jessica J., Tyagi, Samuel C., Uijl, Estrellita, Danser, A. H. Jan, Sawada, Hisashi, Daugherty, Alan, Lu, Hong S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220881/
https://www.ncbi.nlm.nih.gov/pubmed/35740952
http://dx.doi.org/10.3390/biom12060825
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author Ye, Dien
Wu, Congqing
Chen, Hui
Liang, Ching-Ling
Howatt, Deborah A.
Franklin, Michael K.
Moorleghen, Jessica J.
Tyagi, Samuel C.
Uijl, Estrellita
Danser, A. H. Jan
Sawada, Hisashi
Daugherty, Alan
Lu, Hong S.
author_facet Ye, Dien
Wu, Congqing
Chen, Hui
Liang, Ching-Ling
Howatt, Deborah A.
Franklin, Michael K.
Moorleghen, Jessica J.
Tyagi, Samuel C.
Uijl, Estrellita
Danser, A. H. Jan
Sawada, Hisashi
Daugherty, Alan
Lu, Hong S.
author_sort Ye, Dien
collection PubMed
description 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 fludrocortisone 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 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. 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.
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spelling pubmed-92208812022-06-24 Fludrocortisone Induces Aortic Pathologies in Mice Ye, Dien Wu, Congqing Chen, Hui Liang, Ching-Ling Howatt, Deborah A. Franklin, Michael K. Moorleghen, Jessica J. Tyagi, Samuel C. Uijl, Estrellita Danser, A. H. Jan Sawada, Hisashi Daugherty, Alan Lu, Hong S. Biomolecules Brief Report 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 fludrocortisone 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 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. 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. MDPI 2022-06-13 /pmc/articles/PMC9220881/ /pubmed/35740952 http://dx.doi.org/10.3390/biom12060825 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Ye, Dien
Wu, Congqing
Chen, Hui
Liang, Ching-Ling
Howatt, Deborah A.
Franklin, Michael K.
Moorleghen, Jessica J.
Tyagi, Samuel C.
Uijl, Estrellita
Danser, A. H. Jan
Sawada, Hisashi
Daugherty, Alan
Lu, Hong S.
Fludrocortisone Induces Aortic Pathologies in Mice
title Fludrocortisone Induces Aortic Pathologies in Mice
title_full Fludrocortisone Induces Aortic Pathologies in Mice
title_fullStr Fludrocortisone Induces Aortic Pathologies in Mice
title_full_unstemmed Fludrocortisone Induces Aortic Pathologies in Mice
title_short Fludrocortisone Induces Aortic Pathologies in Mice
title_sort fludrocortisone induces aortic pathologies in mice
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220881/
https://www.ncbi.nlm.nih.gov/pubmed/35740952
http://dx.doi.org/10.3390/biom12060825
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