OS 25-01 MR SENSITIVITY IS ENHANCED IN HIGH FAT DIET MICE UNDER EQUALLY-ADJUSTED SALT INTAKE.

OBJECTIVE: It has been reported that obesity-related high blood pressure was partly associated with increased aldosterone secretion and/or activity, but detailed mechanisms are not known. Our previous study suggested that different salt contents in each diet would affect the aldosterone levels. In this study, we investigated the change of aldosterone secretion and MR sensitivity of obesity mice by high fat diet under equally-adjusted salt intake.

DESIGN AND METHOD: We prepared normal fat diet (NFD, 10% lard) and high fat diet (HFD, 60% lard) with equal amount of salt based on the amount of food intake of C57BL/6J mice. The 4-week-old male C57BL/6J mice were fed with NFD or HFD until sacrificed for analysis. Animals were monitored with various physiological parameters and measured plasma renin and aldosterone, urinary albumin, electrolytes, and aldosterone. Messenger RNA levels of steroidogenic enzyme genes in adrenal glands and MR target genes in kidneys were quantitated by real-time RT-PCR assay.

RESULTS: We confirmed that salt intake was equally-adjusted in two groups by measuring amount of food intake and urine sodium excretion. There was no significant difference in plasma aldosterone concentrations between HFD mice and NFD mice at any time point. Cyp11b2 expression was increased in 8-week HFD mice, however, not changed in 16-week and older HFD mice. Body weight and systolic BP were expectedly higher in HFD mice than in NFD mice. Sgk1 expression and urinary albumin were increased in 28-week and 42-week HFD mice compared with NFD mice.

CONCLUSIONS: Sgk1 expression was increased in HFD mice though there was no difference in aldosterone secretion between NFD mice and HFD mice. Our salt-adjusted models in this study revealed that MR sensitivity is enhanced in HFD mice. Therefore they can be good models to study detailed mechanisms of enhanced MR sensitivity in obesity-related hypertension, which is a clinically observed hypertension well-controlled by MR antagonists.