P097 SEXUAL DIMORPHISM IN A HYPERTENSIVE MODEL OF FRUCTOSE PLUS HIGH SALT DIET

High salt diet (HSD) and fructose are both consumed in excess and contributes to hypertension (HTN). Fructose is commonly used to sweeten soft drinks, and studies have linked soft drink consumption to salt-sensitive HTN. However, full mechanisms aren’t understood. Previous data indicates that an acute fructose-enriched diet (FED) increases Na/K/2Cl cotransporter (NKCC2) activity, promoting salt-sensitive HTN in rats; however, there is no research on long-term consumption. Here, our goal was to evaluate whether a FED, coupled to HSD, can induce HTN. Given the known sex-dependent differences in salt-sensitive HTN, we also hypothesized differences between male and female mice. Male and female C57BI/6 mice (10 weeks old, n=4-6) were treated with vehicle or fructose (10% in drinking water) plus HSD (4% in food) for 28 days. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography, and cardiac hypertrophy (morphometry). We performed an acute diuresis test using furosemide to inhibit NKCC2 (20 mg/kg bw, ip) at day 26, and then measured natriuresis (metabolic cages) for 2-hrs. All data are presented by mean standard deviation. Fructose+HSD increased SBP in male mice after 28 days (Veh=110.5±4.6 vs. Frucose+HSD=130.2±5.6 mmHg; p<0.01); in contrast, HTN was completely prevented in female mice (Veh=109.8±6.8 vs. Fructose+HSD=114.0±11.0 mmHg; ns). We did not observe changes in cardiac hypertrophy in either sex. We observed a significant decrease in natriuresis (∼20%) after furosemide injection in male mice (Veh=5.9±1.1 vs. Fructose+HSD=4.7±0.8 μEq/2 h/g bw; ns). Surprisingly, we observed an increase in natriuresis following furosemide injection in female mice (Veh=3.8±5.0 vs. Fructose+HSD= 7.7±2.7 μEq/2 h/g bw; p<0.01). We observed HTN in males following a FED combined with HSD, which was not associated with increased NKCC2 activation. In contrast, female mice showed a resistance to HTN, and yet an apparent increase in NKCC2 activity. This probably suggests a dysregulation of other transporters not evaluated in this work. Finally, we demonstrate that long-term FED, with HSD, induces HTN with a sexual dimorphic effect, apparently through differential renal sodium handling.