Clofibrate prevents and reverses the hemodynamic manifestations of hyperthyroidism in rats.
BACKGROUND
This study analyzed the effects of the chronic administration of clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist, on the development and established hemodynamic, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats.


METHODS
The prevention study used four groups of male Wistar rats: control, clofibrate (240 mg/kg/day by gavage), T(4)(75 microg thyroxine/rat/day s.c.), and T(4)+clofibrate. All treatments were maintained for 3 weeks. Body weight (BW), tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, temperature, SBP, pulse pressure (PP) and HR were recorded in conscious rats, and morphologic, metabolic, plasma, and renal variables were measured. The reversion study used two groups of rats, T(4)(treated for 6 weeks) and T(4)+clofibrate, measuring their hemodynamic variables and temperature for 3 weeks.


RESULTS
T(4) increased BP, HR, PP, and temperature when compared with control rats. Clofibrate prevented and reversed the increase in SBP, HR, PP, and temperature produced by T(4) administration, reduced plasma thyroid hormone levels, and increased plasma thyroid-stimulating hormone values and phenol-uridine diphosphate-glucuronosyl-transferase (UGT) activity. However, clofibrate did not modify the cardiac or renal hypertrophy, polyphagia, polydipsia, or proteinuria of hyperthyroid rats. In normal rats, clofibrate treatment did not significantly change thyroid hormone levels, phenol-UGT activity, or any hemodynamic, morphologic, or renal variables.


CONCLUSIONS
Chronic clofibrate treatment suppressed the hemodynamic manifestations and increased temperature of hyperthyroidism, an effect that can be produced by direct antithyroid effects. However, clofibrate administration did not modify the morphologic, metabolic, or renal alterations of hyperthyroid rats, indicating specificity in the antithyroid actions of clofibrate.
Rodríguez-Gómez
Isabel
I
Departamento de Fisiología, Facultad de Medicina, Granada, Spain.
Cruz
Antonio
A
Moreno
Juan Manuel
JM
Soler
Agatángelo
A
Osuna
Antonio
A
Vargas
Félix
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002994:Clofibrate / Q000494:pharmacology*; D004195:Disease Models, Animal; D014453:Glucuronosyltransferase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006980:Hyperthyroidism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood
D000960:Hypolipidemic Agents; D047493:PPAR alpha; D014284:Triiodothyronine; D014453:Glucuronosyltransferase; D002994:Clofibrate; D013974:Thyroxine