OBJECTIVE: Recent studies have unveiled cardiovascular pathological roles of mineralocorticoid receptor (MR) in many types of cells. Although we have confirmed high expression of MR in intestinal epithelial cells (IEC), that role in progression of cardiovascular diseases is yet to be elucidated. As intestine is the first gate sensing sodium intake, MR of this organ is expected to have essential roles in blood pressure (BP) regulation. This study investigated the role of MR in IEC by using IEC-specific MR knockout mice (IEC-MR KO). DESIGN AND METHOD: We generated IEC-MR KO with floxed MR and Villin Cre mice. We measured BP, body weight and urinary concentration of sodium and potassium. Using eluate of feces, fecal excretion of these electrolytes was also determined. After sacrifice, we quantitated expression level of various genes in intestine and kidney using real-time quantitative RT-PCR assay. Next, we examined the effect of high-salt diet (8% NaCl) and deoxycorticosterone acetate (DOCA)/1% NaCl treatment (1% NaCl solution to drink and DOCA pellet). RESULTS: MR expression of IEC-MR KO decreased by 90% throughout intestine. Compared with wild-type mice (WT), fecal sodium excretion of IEC-MR KO increased by 1.5 fold in accordance with decreased colonic expression of gammaENaC. Conversely, urinary sodium excretion was reduced by 30%. IEC-MR KO exhibited unaltered body weight and BP. DOCA/1% NaCl treatment but not high-salt diet raised BP in both groups. Interestingly, the effect on BP increase in IEC-MR KO was smaller than that of WT (WT: 123.0 +/- 9.0 mmHg, IEC-MR KO: 113.1 +/- 6.0 mmHg, P 〈 0.05). Elevated fecal sodium excretion and decreased urinary excretion in IEC-MR KO were also confirmed. CONCLUSIONS: MR in IEC regulates sodium absorption with modulating gammaENaC expression in colon. The effect of DOCA/1% NaCl treatment on BP was ameliorated with MR deletion from IEC. These studies reveal that intestinal epithelial MR has an important role in regulation of BP.
Type of Publication:
Journal article published