EFFECT OF ESTROGEN ON BLOOD PRESSURE AND RENAL SODIUM HANDLING IN MICE CONSUMING A HIGH SALT AND HIGH FRUCTOSE DIET: A PILOT STUDY
AbstractConsuming high levels of salt and fructose leads to hypertension and obesity in both males and females, but comparatively, the latter appear to be protected against dietary-induced pathologies. The purpose of this study was to determine the effects of 17Î²-estradiol (E2) on blood pressure and renal sodium excretion in mice consuming a diet of high salt and high fructose. Previous studies suggest that E2 administration via a 1.5mg E2 pellet and a 0.05mg E2 pellet in mice provide either too much or too little E2, respectively. This pilot study was designed to analyze the effects induced by a 0.7mg E2 pellet. Ovariectomized CD-1 mice were placed in metabolic cages for 17 days while consuming 4% salt chow with a fluid containing 1% NaCl and 20% fructose. Daily measurements included body weight, food and fluid intake, urine volume, and renal sodium excretion (Nae). Sodium intake (Nai) was determined from food and fluid intake and Nae was calculated by multiplying urine flow rate by urine [Na+]. Molecular expression of renal markers for sodium transport was measured via real-time PCR. Blood pressure was measured via the tail-cuff technique. Mice were divided into two groups: placebo (P) and E2 (n=5/group). No treatment was performed for the first four days of the study, i.e., control period. On the fifth day, pellets (placebo or 0.7mg E2) were implanted subcutaneously for the remainder of the study (i.e., E2 period). Blood pressure was not different between P and E2 mice. Significant results included: 1) body weight was not different at the beginning but decreased in both groups with the P group having higher body weight at the end of the study (p<0.01); 2) the P group consumed more fluid (p<0.0005) and excreted more urine (p<0.01) than the E2 group in the E2 period; 3) average Nae/Nai ratio during the E2 period was lower in the E2 group (p<0.03); and 4) the E2 group had higher mRNA expression of renal cortical NKCC2 (p<0.01) and ENaCÎ² (p<0.005) sodium-transport markers. Results clearly indicate that the 0.7mg E2 pellet induced significant effects on fluid intake, urine output, and renal sodium handling, with no observed pathologies. The 0.7mg pellet appears to provide an effective method of administering E2 in mice for future longer-term studies investigating the many yet-to-be discovered effects of E2 on physiological function.
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