A role of secretin in the control of salt and water homeostasis

Abstract

Secretin (SCT) and its receptor (SCTR) have been shown to play an indispensable role in mediating central actions of angiotensin II (ANGII). More recently, in vivo interactions of their receptors, SCTR and AT1aR, have implicated to stimulate hyperosmolality-induced water intake in rodents. It remains unknown whether the SCT/SCTR axis is also involved in regulating peripheral actions of ANGII, including aldosterone biosynthesis and release. In this study, C57BL/6N (WT) and SCTR knockout (SCTR-/-) mice were fed either standard (0.3% Na+) or low Na+ (0.03% Na+) chow for 20 days, and plasma levels of ANGII, SCT and aldosterone were determined. Sodium restriction resulted in significantly elevated plasma levels of ANGII, SCT and aldosterone in WT, while only ANGII was increased in SCTR-/-. Consistently, under sodium restriction, augmented zona glomerulosa (ZG) layer thickness as well as aldosterone synthase (CYP11B2) transcript and protein levels were found in adrenal glands of WT, but not in SCTR-/-. Although the plasma cholesterol concentrations in WT and SCTR-/- were similar, the transcript of high-density-lipoprotein (HDL) cholesterol receptor (scavenger receptor BI) was increased only in WT under sodium restriction. Furthermore, the accumulation of cholesterol, the precursor of aldosterone, was not observed in the adrenal glands of SCTR-/- fed with low Na+ chow. Taken together, the knockout of SCTR resulted in defective aldosterone biosynthesis/release, and the SCT/SCTR axis is required for aldosterone precursor uptake, expression of CYP11B2 and ZG hyperplasia under sodium restriction in mouse.