Contribution of Renal Epithelial Na Channel (ENaC) in Clofibrate‐mediated Reduction in Blood Pressure in Female SHR

Abstract

Renal epithelial sodium channels (ENaC) of the collecting duct (CD) play an important role in electrolyte transport and blood pressure (BP) regulation. ENaC activity and expression are greater in hypertension. Clofibrate (CF), a PPARα ligand, increased excretion of Na+ (UNaV) and nitrite (UNOxV) but reduced elevated BP. This study tested the hypothesis that ENaC plays no role in CF-induced alteration in Na+ transport in SHR. Female WKY and SHR rats were treated with CF (250 mg/kg) or vehicle for 7 days followed by benzamil (BM: 0.7 mg/kg), an inhibitor of ENaC. Peroxisomal β-oxidation was higher in SHR (20%) as was PPARα expression (35%) compared to WKY rats. CF increased β-oxidation and PPARα expression in WKY and SHR. CF reduced BP in SHR (11%) but not in WKY rats. Basal UNaV (4 hr) was higher in SHR (50%) and CF reduced UNaV (23%) in WKY rats but not in SHR. BM alone increased UNaV more markedly in SHR (245 vs, 18% WKY) but equally accentuated it in CF-treated WKY and SHR (2–4 fold). CF increased (2–3 fold) UNOxV in WKY and SHR but BM blunted CF-mediated increase in NO production which was more marked in SHR. ENaC protein expression was higher (33%) in SHR and CF enhanced ENaC expression in WKY but not in SHR. These data suggest that CF increased PPARα expression and reduced the elevated BP in female SHR without affecting ENaC expression or its activity consistent with a lack of PPARα expression in the CD, the primary site of action of ENaC.