Secretin is involved in sodium conservation through the renin‐angiotensin‐aldosterone system

Secretin (SCT) and its receptor (SCTR) are important in fluid regulation at multiple levels via the modulation of expression and translocation of renal aquaporin 2 and functions of central angiotensin II (ANGII). The functional interaction of SCT with peripheral ANGII, however, remains unknown. As the ANGII‐aldosterone axis dominates the regulation of renal epithelial sodium channel (ENaC) function, we therefore tested whether SCT/ SCTR can regulate sodium homeostasis via the renin‐angiotensin‐aldosterone system. SCTR‐knockout (SCTR −/− ) mice showed impaired aldosterone synthase (CYP11B2) expression and, consequently, aldosterone release upon intraperitoneal injection of ANGII. Endogenous ANGII production induced by dietary sodium restriction was higher in SCTR −/− than in C57BL/6N wild‐type (WT) mice, but CYP11B2 and aldosterone synthesis were not elevated. Reduced accumulation of cholesteryl ester—the precursor of aldosterone—was observed in adrenal glands of SCTR −/− mice that were fed a low‐sodium diet. Absence of SCTR resulted in elevated basal transcript levels of adrenal CYP11B2 and renal ENaCs. Although transcript and protein levels of ENaCs were similar in WT and SCTR −/− mice under sodium restriction, ENaCs in SCTR −/− mice were less sensitive to amiloride hydrochloride. In summary, the SCT/ SCTR axis is involved in aldosterone precursor uptake, and the knockout of SCTR results in defective aldosterone biosynthesis/release and altered sensitivity of ENaCs to amiloride. —Bai, J., Chow, B. K. C. Secretin is involved in sodium conservation through the renin‐angiotensin‐aldosterone system. FASEB J . 31, 1689–1697 (2017) www.fasebj.org