Sex differences in blood pressure and renal handling of sodium in mice on a high salt and high fructose diet

Abstract

Background: High consumption of either fructose or salt can have deleterious consequences on health and consuming high levels of both leads to serious health problems. Research demonstrates that important sex differences exist with respect to renal metabolism of high fructose intake which directly effects renal handling of sodium. The objective of this study was to investigate sex differences in blood pressure and renal handling of sodium in mice consuming a high-salt and high-fructose (HSHF) diet. We set out to determine if females are protected from high blood pressure when consuming HSHF.

Methods: Healthy 4-week-old male and female mice (n=6/group) were placed in metabolic cages for six weeks. For the first week (baseline), all mice consumed a normal diet (0.25% salt) with water. Mice were then placed on the HSHF diet consisting of 4% salt chow with a drinking solution of 20% fructose and 1% NaCl for the next 4 weeks. This was followed by a recovery week with mice on the normal diet with water. Blood pressure was measured daily via the tail cuff technique and averaged weekly. Daily measurements of sodium intake and output were measured. Sodium intake (Nai, mEq/day) was calculated from daily food and fluid consumptionand output was measured by sodium excretion (Nae, mEq/day) (urine volume, ml/day x urine sodium concentration, mEq/day). Sodium concentration was measured using the EasyLyte Na/K analyzer. The ratio Nae/Nai indicates sodium retention. Real-time PCR was conducted using custom-made PCR arrays made by Qiagen SA Biosciences) designed with specific primers for mouse renal Na+ transporters.

Results: Mean blood pressure (MBP) was not different between male and female mice in the baseline week and in the first week on HSHF diet. MBP significantly increased in female mice in the 2nd week on the HSHF diet whereas MBP increased in male mice only slightly from baseline. In the 3rd week on HSHF diet male MBP increased to that of the females and MBP in both sexes remained high in the 4th week. In the recovery week, MBP remained elevated in females whereas MBP in males decreased significantly (p<0.01 compared to females). Female mice showed higher sodium retention during the HSHF period via the Nae/Nai (62±5% vs 75±5%, p<0.001). Molecular expression of renal sodium transporters showed significantly higher expression of the NKCC and the NCC transporter in the female kidney.

Conclusion: Results indicate that the HSHF diet significantly increased MBP in female and male mice. MBP in females increased before that in males and remained elevated during the recovery period whereas blood pressure decreased in males in the recovery period. Females had higher retention of sodium and higher expression of renal sodium transporters. We conclude that female mice are not protected from the HSHF dietary-induced increase in blood pressure. This study challenges the current position that females possess protective mechanisms against dietary induced increase in blood pressure.