Abstract 328: High Fructose but not High Glucose Intake Induces Salt-sensitive Hypertension and Enhances NKCC2 Phosphorylation in Normal Rats.

Abstract

Consumption of fructose as a sweetener has increased in the past three decades. A high-fructose diet has been implicated in the epidemic of diabetes, obesity, and hypertension. A third of the US population consumes 20-40% of their caloric intake from added sugars, with half of those calories from fructose. Little is known about the role of high fructose intake in renal salt handling and blood pressure regulation during high salt intake. In genetic models of salt-sensitive hypertension, the Na/K/2Cl cotransporter NKCC2 plays an important role by reabsorbing NaCl in the thick ascending limb (TAL). We hypothesized that 20% fructose in drinking water stimulates NKCC2 and sensitizes normal rats to high salt induced hypertension. Adult Sprague-Dawley rats were given 20% fructose or 20% glucose in drinking water for 1 week after which a high salt diet (4% Na in chow) was started. Systolic blood pressure (SBP) was measured every other day by tail cuff after 2 weeks of training. After one week of fructose or glucose alone, SBP did not change. In rats fed fructose, adding a 4% NaCl diet increased SBP to 128±6 mmHg by day 2 (p<0.01 vs glucose) and continued to increase up to 144±18 mmHg after 2 weeks on high salt (p<0.01 vs baseline; p<0.01 vs glucose). In glucose-fed rats high salt did not increase SBP (from 122±6 to 116±9 mmHg). 20% fructose alone for 3 weeks, or high salt alone did not change SBP. NKCC2 phosphorylation at Thr96,101 is associated with enhanced TAL NaCl reabsorption. We found that NKCC2 phosphorylation at Thr96,101 (normalized to total NKCC2) was higher in TALs isolated from rats fed fructose plus salt for 2 weeks compared to high salt alone (high-salt: 100%; fructose + high-salt: 250±40%, p<0.05). We concluded that a high fructose but not high glucose diet induces salt-sensitive hypertension in Sprague Dawley rats. This effect occurs within 1 week of a high fructose diet. In addition, a high fructose diet may stimulate NKCC2 activity by enhancing its phosphorylation. These data suggest that high fructose intake may increase blood pressure by preventing appropriate renal NaCl excretion during high dietary salt intake.