Abstract 045: High Fat Diet Increases Blood Pressure In Sprague Dawley Rats And Induces Salt Sensitive Hypertension: Role Of NKCC2 In The Thick Ascending Limb (TAL)

Abstract

The Western Diet is characterized by elevated added sugars, fat, and salt and is known to promote hypertension. Chronic high fat intake induces obesity in rodents but the effects on blood pressure are variable between rat/mouse strains. The early effects of a high fat diet, prior to the onset of obesity, in kidney function, signaling and NaCl reabsorption have been poorly studied. In the kidneys, the thick ascending limb (TAL) absorbs 25% of filtered NaCl through the apical Na/K/2Cl cotransporter NKCC2. NKCC2 is activated by phosphorylation at residues Thr 96,101 , or Ser 126 or by increasing its trafficking to the apical surface. The effects of a high fat diet on NKCC2 activity and blood pressure have been poorly studied in the Sprague Dawley (SD) rat, a widely used rodent model. We hypothesized that a high fat diet (60%kCal saturated fat, HF) activates NKCC2 and induces salt sensitive hypertension. We first tested the effects HF on blood pressure (BP). SD rats (Charles Rivers) were trained for tail cuff SBP and placed on HF or control diet for 4 weeks. After 2 weeks, HF diet increased SBP by 9±4 mmHg and at 4 weeks by 13±4 mmHg (p<0.05). We then added high salt diet (4% Na, HS, n=7) which further increased SBP by 19±5 mmHg in HF rats reaching 151±5 mmHg after 4 weeks. SBP did not change in rats fed HS or HF alone (HS: 121±4, HF: 132±4 mmHg, p<0.05 vs HF+HS). In isolated TALs, 2 weeks of HF did not change total NKCC2 expression or P-Thr 96,101 , but enhanced P-Ser 126 NKCC2 (78±26%, p<0.05) and increased surface/intracellular NKCC2 ratio by 22±8% (p<0.03). After 8 weeks of HF diet, surface to intracellular NKCC2 was higher in HF (+54±9% from HS, p<0.05) and HF+HS rats (+40±18% of HS) compared to those fed HS alone. Body weight gain was similar in groups after 2 weeks, but after 8 weeks, rats on HF or HF+HS gained more weight than HS alone (p<0.05). Blood glucose was not different between groups. Our data suggest that 2 weeks of a HF diet induces early signaling in TALs, prior to obesity, that may contribute to increase BP or induce salt sensitivity in normal rats.