Dietary Fructose Increases the Sensitivity of Proximal Tubules to Angiotensin II in Rats Fed High-Salt Diets

Dietary fructose causes salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the filtered NaCl. Angiotensin II (Ang II), atrial natriuretic peptide (ANP) and norepinephrine (NE) regulate this process. Although Ang II signaling blockade ameliorates fructose-induced salt-sensitive hypertension, basal PT Na(+) reabsorption and its sensitivity to the aforementioned factors have not been studied in this model. We hypothesized consuming fructose with a high-salt diet selectively enhances the sensitivity of PT transport to Ang II. We investigated the effects of Ang II, ANP and NE on PT Na reabsorption in rats fed a high-salt diet drinking tap water (HS) or 20% fructose (HS-FRU). Oxygen consumption (QO(2)) was used as a measure of all ATP-dependent transport processes. Na(+)/K(+)-ATPase and Na(+)/H(+)-exchange (NHE) activities were studied because they represent primary apical and basolateral transporters in this segment. The effect of 10(−12) mol/L Ang II in QO(2) by PTs from HS-FRU was larger than HS (p < 0.02; n = 7). In PTs from HS-FRU 10(−12) mol/L Ang II stimulated NHE activity by 2.6 ± 0.7 arbitrary fluorescence units/s (p < 0.01; n = 5) but not in those from HS. The stimulatory effect of Ang II on PT Na(+)/K(+)-ATPase activity was not affected by HS-FRU. Responses of QO(2) and NHE activity to ANP did not differ between groups. The response of QO(2) to NE was unaltered by HS-FRU. We concluded that the sensitivity of PT Na(+) reabsorption specifically to Ang II is enhanced by HS-FRU. This maintains high rates of transport even in the presence of low concentrations of the peptide, and likely contributes to the hypertension.