Modulation Of Proximal Na+ Reabsorption Is Related To The Fructose-Induced Hypertension

Methods/Results: Wistar rats were fed for 2 or 8 weeks with control diet (CTRL) or isocaloric 60% fructose diet (HF). Systolic blood pressure (SBP) was measured weekly by tail cuff plethysmography. There was no difference in the SBP after 2 weeks; however, there was an increase in SBP after 8 weeks (P < 0.0001). 24h urine collected in metabolic cages showed a reduction in urine flow (2 weeks - P = 0.0007 and 8 weeks - P = 0.001). Glomerular filtration rate (GFR) was not altered after 2 weeks, but was decreased after 8 weeks (P = 0.001). Na+ fractional excretion (FE) was decreased after 2 weeks (P = 0.0131), but was increased after 8 weeks (P = 0.038). After 2 or 8 weeks, rats were subjected to in situ microperfusion experiments and had their proximal tubules (TP) perfused with an alkaline solution to investigate Na+ reabsorption by means of bicarbonate flux (JHCO3-, in nmol/cm2 x s). JHCO3- was increased after 2 weeks (P < 0.0001) but was reduced after 8 weeks (P < 0.0001). Perfusion using S3226, a specific NHE3 inhibitor, showed that fructose acts stimulating NHE3 activity after 2 weeks (P < 0.0001) and inhibiting it after 8 weeks (P < 0.0001). Conclusions: Reduced Na+ FE and urine flow, associated with increased NHE3 activity after 2 weeks of HF suggest that initially fructose leads to a state of Na+ overload, which may contribute to the development of hypertension observed after 8 weeks of HF intake. Kidney damage was increased after 8 weeks, since GFR was decreased, explaining the persistence of reduced urine flow, despite reduced NHE3 activity. These data suggest that the mechanism of pressure-natriuresis was activated after 8 weeks, in order to compensate for volume expansion.