PPARgamma Modulates the Sodium Transporters in the Renal Proximal Tubule Epithelium in Vivo and in Vitro

• Published in: The FASEB journal 2007, Vol.21 (6), p.A901-A901
• Main Authors: Ambrozewicz, Marta, DeBose, Sophia Chung, Duran‐Simsek, Fatma, Ali, Khraibi Amin, Dobrian, Anca Dana
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A901

Our hypothesis is that activation of PPARγ reduces blood pressure (BP) in obesity hypertension by decreasing expression of proximal tubule sodium transporters NHE3 and Na, K‐ATPase. The aim of this study was to determine: the effect of PPARγ activation on protein expression of the sodium transporters in vivo and in vitro and, the role of NO as a potential mediator of PPARγ effect. Obesity‐prone (OP) and obesity‐resistant (OR) rats were treated with pioglitazone (Pio) or Pio and L‐NAME, for 4 weeks. Also, cultures of human renal proximal tubule cells (RPTEC) were stimulated with Pio with or without L‐NAME. BP was increased and sodium excretion decreased in OP vs OR rats. Pio normalized BP and increased sodium excretion in OP rats and addition of L‐NAME blunted these effects. NO was elevated in both groups treated with Pio. In OP rats, expression of Na,K‐ATPase was increased by Pio treatment and reversed by L‐NAME. Also, Pio treatment reduced expression of NHE3 in both the OP and OR rats and L‐NAME addition had no further effect. RPTEC treated with Pio showed a decrease in NHE3 and Na, K‐ATPase expression. Addition of L‐NAME did not affect expression of NHE3, but blunted the reducing effect of Pio on Na,K ATPase expression. Collectively, the results show that PPARγ activation reduces BP by an increase in natriuresis. This effect is achieved, at least in part, by the modulation of the sodium transporters and NO plays a significant role.