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.
Highlights
Globalization and economic growth made processed foods available throughout the world [1].Modern diets are rich in NaCl and in fructose or fructose-containing syrups used as sweeteners [1]
Food intake was lower in HS-FRU, the difference in calories was made up by the calories consumed as fructose
700 mEq/kg Na+, 200 g/Kg fructose in the drinking water: (1) increased blood pressure; (2) enhanced the ability of a low concentration of Angiotensin II (Ang II) to stimulate QO2, which was due to a primary elevation of Na+ /H+ exchangers (NHEs) activity rather than Na+ /K+ -ATPase; and (3) did not alter the response of the proximal nephron to atrial natriuretic peptide (ANP) or NE
Summary
Globalization and economic growth made processed foods available throughout the world [1]. Cross sectional studies using questioners to estimate fructose intake, associate elevated chronic consumption of this sugar with hyperuricemia [14], insulin resistance [15] and increased cardiovascular risk [16,17] Those individuals consuming more than 74 g/day of fructose, equivalent to about 15% caloric intake on a 2000 kcal/day diet, present higher blood pressure values [17]. We reported that dietary fructose in the absence of a high-salt diet enhances the sensitivity of proximal nephron Na+ transport to the stimulatory effect of Ang II [38]. Blunting the actions of NE reduces the detrimental renal effects caused by dietary fructose [51] It is unknown whether such diets enhance the sensitivity of proximal nephron Na+ reabsorption to NE similar to Ang II.
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