Effect of Clofibrate in the Regulation of Blood Pressure in Spontaneously Hypertensive Rats.

Abstract

Peroxisome Proliferator Activated Receptors (PPARs) are nuclear transcription factors that regulate numerous genes influencing blood pressure. Previously we have shown that induction of PPARα by clofibrate increased nitric oxide (NO) production and reduced blood pressure in DOCA-salt hypertension. In this study, we examined the contribution of PPARα to the regulation of blood pressure in spontaneously hypertensive rats (SHR). WKY and SHR rats were randomly allocated into groups treated with vehicle or clofibrate, a PPARα ligand (250 mg/kg i.p. for 2 months). Systolic blood pressure (SBP) was measured before and after the study period using tail-cuff plethysmography. Rats were sacrificed under anesthesia and urine and tissue samples were processed for subsequent analysis. SBP was higher in SHR (198±6 mmHg) compared with WKY rats (93±7mmHg) and was associated with a 3-fold increase in urinary protein excretion. Clofibrate reduced SBP (26±2%) and proteinuria (45±9%) in SHR but not in WKY rats. In SHR, urinary nitrite/nitrate excretion was ~2- fold greater (vs. WKY) and was further increased by clofibrate treatment by 30±4% and 48±3%, respectively. In addition, PPARα protein expression was reduced in SHR kidneys compared to WKY rats. However, clofibrate did not increase PPARα protein expression significantly in either WKY or SHR. This study suggests that PPARα contributes to regulation of blood pressure in SHR and that clofibrate-mediated reduction in blood pressure and proteinuria in SHR probably through increased NO production.