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Contribution of Renal Epithelial Na Channel (ENaC) in Clofibrate‐mediated Reduction in Blood Pressure in Female SHR
Author(s) -
Yousefipour Zivar,
Butler Robyn,
Newaz Mohammad,
Oyekan Adebayo
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb123-c
Subject(s) - medicine , endocrinology , epithelial sodium channel , clofibrate , chemistry , blood pressure , excretion , sodium , organic chemistry
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 + (U Na V) and nitrite (U NOx V) 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 U Na V (4 hr) was higher in SHR (50%) and CF reduced U Na V (23%) in WKY rats but not in SHR. BM alone increased U Na V 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) U NOx V 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.