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Nutrients 2018, 10(9), 1244; https://doi.org/10.3390/nu10091244

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

1
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
2
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina
3
Facultad de Medicina, Departamento de Ciencias Fisiológicas, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1121ABG, Argentina
4
Merk Research Laboratories, 630 Gateway Blvd, South San Francisco, CA 94080, USA
5
Instituto de Química y Fisicoquímica Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1113AAD, Argentina
*
Author to whom correspondence should be addressed.
Received: 8 August 2018 / Revised: 4 September 2018 / Accepted: 5 September 2018 / Published: 6 September 2018
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Abstract

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 (QO2) 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 QO2 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 QO2 and NHE activity to ANP did not differ between groups. The response of QO2 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. View Full-Text
Keywords: kidney; blood pressure; salt sensitivity; Na+/H+ exchange; Na+/K+-ATPase; atrial natriuretic peptide; norepinephrine; sodium excretion kidney; blood pressure; salt sensitivity; Na+/H+ exchange; Na+/K+-ATPase; atrial natriuretic peptide; norepinephrine; sodium excretion
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Gonzalez-Vicente, A.; Hong, N.J.; Yang, N.; Cabral, P.D.; Berthiaume, J.M.; Dominici, F.P.; Garvin, J.L. Dietary Fructose Increases the Sensitivity of Proximal Tubules to Angiotensin II in Rats Fed High-Salt Diets. Nutrients 2018, 10, 1244.

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