Short-Term High-Salt Diet Increases Corin Level to Regulate the Salt–Water Balance in Humans and Rodents

Abstract

BACKGROUND

Dietary sodium and potassium affect the fluctuation in blood pressure (BP) and renal function. Corin, with its enzymatic activity to convert pro-atrial natriuretic peptide (pro-ANP) to biologically active ANP, regulates BP, cardiac, and renal functions. We investigated whether corin expression responds to a high-salt (HS) diet to regulate salt and water balance.

METHODS

Forty-two volunteers followed 3 sequential diets for 7 days each: a low-salt (LS) diet (3.0 g/day NaCl), a HS diet (18.0 g/day NaCl), followed by an HS diet with K⁺ supplementation (HS + K⁺) (18.0 g/day NaCl and 4.5 g/day KCl).

RESULTS

Corin level was higher with the HS diet than the LS and HS + K⁺ diets and was positively correlated with systolic BP (SBP) and 24-hour urinary Na⁺ and microalbumin (U-mALB) excretion. In rodents, serum and renal levels of corin were transiently increased with the HS diet and were decreased if the HS diet was continued for up to 7 days. HS loading increased SBP, 24-hour urinary Na⁺, U-mALB excretion, and the expression of proprotein convertase subtilisin/kexin-6 (PCSK6), a corin activator. Knockdown of PCSK6 or corin in high salt-treated M1-cortical collecting duct (M1-CCD) cells increased the expression of aquaporin 2 (AQP2) and β-epithelial Na⁺ channel (β-ENaC).

CONCLUSIONS

Short-term HS may induce the PCSK6–corin–ANP–AQP2/β-ENaC pathway in the kidney. Enhanced serum corin level in humans and rodents is positively correlated with HS-induced SBP and 24-hour urinary Na⁺ and U-mALB excretion, which suggests that corin is involved in the salt-water balance in response to HS intake.

CLINICAL TRIALS REGISTRATION

Public Trials Registry Number NCT02915315

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