Background: Hyperthyroidism promotes the development and progression of cardiovascular
diseases (CVD). Aldosterone, a key mediator of myocardial inflammation, oxidative stress and fibrosis,
may be activated in hyperthyroidism.
Objective: To assess the impact of hyperthyroidism on aldosterone levels and myocardial oxidative
status, inflammatory and fibrotic markers in hyperthyroid rats, and to test if the use of spironolactone
(an aldosterone antagonist) attenuates these changes.
Methods: Adult Wistar rats were randomly distributed into 4 groups; controls, spironolactone treated
rats (Spir, 50mg/kg/day), hyperthyroid rats (Hyper, daily intraperitoneal levothyroxine 0.3mg/kg/day),
and spironolactone treated hyperthyroid rats (Hyper+Spir) for 4 weeks. Blood pressure (Bp), and levels
of serum and myocardial aldosterone, oxidants/antioxidants, inflammatory and fibrotic markers were
Results: Levothyroxine increased serum thyroid hormones and increased Bp, heart rate and heart to
bodyweight ratio. Relative to control, serum aldosterone levels were increased in Hyper and Hyper+
Spir groups. In parallel, cardiac lipid peroxides and serum endothelin-1 were increased whereas
cardiac superoxide dismutase, catalase, glutathione, and matrix metalloproteinase -2 were reduced in
the Hyper group. Spironolactone decreased serum thyroid hormones and improved cardiac lipid peroxides
and metalloproteinase -2 levels. The use of spironolactone decreased serum nitrite levels and increased
cardiac SOD and glutathione. Cardiac levels of aldosterone, endothelin-1, transforming growth
factor-beta and nitrite were similar among all groups.
Conclusion: Hyperthyroid status was associated with an increase in aldosterone and oxidant/
inflammatory biomarkers. The use of spironolactone enhanced antioxidant defenses. Aldosterone
antagonists may serve as potential drugs to attenuate the development of cardiac disease in hyperthyroidism.