Independent Effects of Sex and Stress on Fructose-induced Salt-sensitive Hypertension

Proximal tubule fructose metabolism is key to fructose-induced hypertension, but the roles of sex and stress are unclear. We hypothesized that females are resistant to the salt-sensitive hypertension caused by low amounts of dietary fructose compared to males and that the magnitude of the increase in blood pressure (BP) depends, in part, on amplification of the stress response of renal sympathetic nerves. We measured systolic BP (SBP) in rats fed high salt with either no sugar (HS), 20% glucose (GHS) or 20% fructose (FHS) in the drinking water for 7-8 days. FHS increased SBP in both males (Δ22 ± 9 mmHg; p < 0.046) and females (Δ16 ± 3 mmHg; p < 0.0007), while neither GHS nor HS alone induced changes in SBP in either sex. The FHS-induced increase in SBP as measured by telemetry in the absence of added stress (8 ± 2 mmHg) was significantly lower than that measured by plethysmography (24 ± 5 mmHg) (p < 0.014). However, when BP was measured by telemetry simulating the stress of plethysmography, the increase in SBP was significantly greater (15 ± 3 mmHg) than under low stress (8 ± 1 mmHg) (p < 0.014). Moderate-stress also increased telemetric diastolic (p < 0.006) and mean BP (p < 0.006) compared to low-stress in FHS-fed animals. Norepinephrine excretion was greater in FHS-fed rats than HS-fed animals (Male: 6.4 ± 1.7 vs.1.8 ± 0.4 nmole/kg/day; p < 0.02. Female 54 ± 18 vs. 1.2 ± 0.6; p < 0.02). We conclude that fructose-induced salt-sensitive hypertension is similar in males and females unlike other forms of hypertension, and the increase in blood pressure depends in part on an augmented response of the sympathetic nervous system to stress.