Effects of Clofibrate on Salt Loading‐Induced Hypertension in Rats

Antonio Cruz,Juan Manuel Moreno,Andrés Quesada,Isabel Rodríguez-Gómez,Rosemary Wangensteen,Rocío Pérez-Abud,Antonio Osuna,Miguel Ángel Vargas

doi:10.1155/2011/469481

Abstract

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T4 (FT4) and tissue FT4 and FT3 versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels.

Highlights

Fibrates are synthetic agonists of peroxisome proliferatoractivated receptor-α (PPARα), a subfamily of the nuclear receptor superfamily naturally activated by ligands such as free fatty acids and eicosanoids [1]
Saline loading produced an increase in systolic blood pressure (SBP) and heart rate (HR) and pulse pressure (PP) in comparison to control rats
Clofibrate administration to normal rats at the dose and time used in this experiment produced a modest but significant decrease in blood pressure (BP) (4.8 ± 0.6 mmHg) and HR (16 ± 5.7 beats/min)

Summary

Introduction

Fibrates are synthetic agonists of peroxisome proliferatoractivated receptor-α (PPARα), a subfamily of the nuclear receptor superfamily naturally activated by ligands such as free fatty acids and eicosanoids [1]. Fibrates have been in clinical use as hypolipidemic agents for several decades. They have been reported to have beneficial effects on cardiovascular function [1,2,3] and elevated BP [4, 5]. The molecular mechanisms of the negative interaction between thyroid hormone and PPARs include an increase in thyroid hormone deactivation [9] and reductions in the gene expression of their transporters [10,11,12] and in the activity of deiodinases [10] and action [6, 8, 10,11,12]. Clofibrate treatment markedly reduced plasma thyroid hormone levels and increased tissue activity of phenol-UGT, an enzyme that deactivates thyroid hormones in chronically treated hyperthyroid rats [13]

Methods

Results

Conclusion