title: Clofibrate prevents and reverses the hemodynamic manifestations of hyperthyroidism in rats.
abstract: 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez-Gómez
authors.forename: Antonio
authors.initials: A
authors.lastname: Cruz
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Moreno
authors.forename: Agatángelo
authors.initials: A
authors.lastname: Soler
authors.forename: Antonio
authors.initials: A
authors.lastname: Osuna
authors.forename: Félix
authors.initials: F
authors.lastname: Vargas
mesh_terms: 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
chemical_list: D000960:Hypolipidemic Agents; D047493:PPAR alpha; D014284:Triiodothyronine; D014453:Glucuronosyltransferase; D002994:Clofibrate; D013974:Thyroxine