Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide

Previously, we reported that 20% fructose diet causes salt-sensitive hypertension. In this study, we hypothesized that a high salt diet supplemented with 20% fructose (in drinking water) stimulates salt-sensitive hypertension by increasing salt retention through decreasing renal nitric oxide. Rats in metabolic cages consumed normal rat chow for 5days (baseline), then either: (1) normal salt for 2weeks, (2) 20% fructose in drinking water for 2weeks, (3) 20% fructose for 1week, then fructose + high salt (4% NaCl) for 1week, (4) normal chow for 1week, then high salt for 1week, (5) 20% glucose for 1week, then glucose + high salt for 1week. Blood pressure, sodium excretion, and cumulative sodium balance were measured. Systolic blood pressure was unchanged by 20% fructose or high salt diet. 20% fructose+high salt increased systolic blood pressure from 125 +/- 1 to 140 +/- 2mmHg (P < 0.001). Cumulative sodium balance was greater in rats consuming fructose+high salt than either high salt, or glucose+high salt (114.2 +/- 4.4 vs. 103.6 +/- 2.2 and 98.6 +/- 5.6mEq/Day19; P < 0.05). Sodium excretion was lower in fructose + high salt group compared to high salt only: 5.33 +/- 0.21 versus 7.67 +/- 0.31mmol/24h; P < 0.001). Nitric oxide excretion was 2935 +/- 256mol/24h in high salt-fed rats, but reduced by 40% in the 20% fructose + high salt group (2139 +/- 178mol/24hrs P < 0.01). Our results suggest that fructose predisposes rats to salt-sensitivity and, combined with a high salt diet, leads to sodium retention, increased blood pressure, and impaired renal nitric oxide availability.