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Fludrocortisone Induces Aortic Pathologies in Mice.

Dien Ye1,2, Congqing Wu1,3, Hui Chen1

  • 1Saha Cardiovascular Research Center, Lexington, KY 40536, USA.

Biomolecules
|June 24, 2022
PubMed
Summary

Fludrocortisone treatment caused aortic pathologies in mice, including aneurysms and ruptures, independent of cholesterol levels. This suggests a potential risk of aortic disease in individuals using fludrocortisone.

Keywords:
angiotensinaortic aneurysmsaortic dissectionfludrocortisonehypercholesterolemiamouse

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Area of Science:

  • Cardiovascular Science
  • Endocrinology
  • Pharmacology

Background:

  • Fludrocortisone is used to treat conditions like Addison's disease and orthostatic hypotension.
  • High blood pressure is a known side effect of fludrocortisone therapy.
  • Aortic aneurysms were unexpectedly observed in mice during fludrocortisone-induced hypertension studies.

Purpose of the Study:

  • To investigate if fludrocortisone induces aortic pathologies.
  • To determine if these pathologies occur in both normocholesterolemic and hypercholesterolemic mice.
  • To assess the impact of fludrocortisone on aortic health across different mouse models.

Main Methods:

  • Male C57BL/6J mice were infused with fludrocortisone or vehicle for 28 days.
  • Fludrocortisone was administered to ApoE-/- and LDL receptor-/- mice on varying diets.
  • Systolic blood pressure and aortic pathologies (hemorrhage, dilation, wall thickening/thinning) were assessed.

Main Results:

  • Fludrocortisone increased systolic blood pressure in all mouse models.
  • Aortic pathologies, including ascending/arch and thoracic/abdominal issues, were observed in fludrocortisone-treated mice.
  • Two mice on a Western diet experienced aortic rupture, and ascending aortic diameter was significantly increased in this group.

Conclusions:

  • Fludrocortisone induces aortic pathologies independently of hypercholesterolemia.
  • The findings suggest a potential increased risk of aortic pathologies in humans taking fludrocortisone.
  • Further research is warranted to elucidate the precise mechanisms and clinical implications.