A Fructose‐Enriched Diet Induces Salt‐Sensitive Hypertension and Enhances NKCC2 and SPAK/OSR1 Phosphorylation in Thick Ascending Limbs (TALs).

Abstract

Fructose consumption increased in the past three decades and has been implicated in the epidemic of hypertension, diabetes and obesity. 10% of the US population consumes up to 20% of their calories from fructose. The effect of fructose intake in sodium handling by the kidney and blood pressure regulation is not understood. In models of salt-sensitive hypertension, the Na-K-2Cl cotransporter (NKCC2) presents higher activity. We hypothesized that 20% fructose (but not glucose) induces salt sensitive hypertension in part by enhancing NKCC2 activity. Sprague-Dawley rats were given 20% fructose or 20% glucose in drinking water for 1 week after which high salt diet (4% Na in chow) was started. Systolic blood pressure (SBP) was measured by tail cuff. In fructose-fed rats, the addition of 4% NaCl diet increased SBP from 120±10 to 128±6 mmHg on day 2 (p<0.01) and to 144±18 mmHg after 2 weeks (p<0.01). In rats fed glucose or high salt alone SBP was not changed. NKCC2 phosphorylation at Thr96,101 was enhanced by 161±51% (p<0.02) in rats fed fructose plus salt compared to salt alone and phospho-Ser126 was also enhanced by 151±40%. The phosphorylation of SPAK/OSR1 kinases was enhanced by 100±30% (p<0.04). Furosemide sensitive NaCl transport in TALs was enhanced by 36±11% in rats fed fructose plus high salt compared to salt alone (p<0.02). We concluded that a high fructose but not high glucose diet induces salt-sensitive hypertension in normal rats. The salt sensitivity may be in part due to higher NKCC2 phosphorylation and activity which was maintained during high salt intake.