Influence of serum chloride concentrations on the renin-angiotensin-aldosterone system in dogs with congestive heart failure.

Authors

Darcy Adin, Yang Qu, Oliver Domenig, Autumn Harris

Published in

American journal of physiology. Renal physiology. Jun 21, 2026. Epub Jun 21, 2026.

Abstract

Chloride is a key determinant of macula densa signaling and renin release, but its relationship with systemic renin-angiotensin-aldosterone system (RAAS) activity in naturally occurring heart failure is incompletely defined. We evaluated associations between serum chloride concentration and circulating RAAS metabolites in 147 dogs (20 healthy, 39 preclinical heart disease, 88 congestive heart failure [CHF]). Circulating angiotensin metabolites, aldosterone, and ACE and ACE2 activity were quantified by liquid chromatography-mass spectrometry. Associations between serum chloride and RAAS components were assessed using HC3 robust multivariable linear regression adjusted for sex, ACE inhibitor use, and serum bicarbonate. Dogs with CHF had higher circulating RAAS metabolites than healthy and preclinical dogs. Serum chloride was inversely correlated with multiple RAAS metabolites, including Ang I (rₛ = -0.515) and Ang 1-7 (rₛ = -0.546; both P < 0.0001). Lower serum chloride was independently associated with higher concentrations of angiotensin peptides (Ang I, II, III, IV, and Ang 1-7) and aldosterone, with each 5 mmol/L decrease corresponding to 32-45% increases in angiotensin metabolites and a 39% increase in aldosterone (all adjusted P ≤ 0.02). Hypochloremia (<100 mEq/L) identified a distinct RAAS phenotype characterized by higher downstream angiotensin metabolites, including Ang II, III, and IV (all adjusted P ≤ 0.03). Chloride was not associated with ACE or ACE2 activity. Serum chloride is independently associated with systemic RAAS activation in dogs with heart disease, supporting an association between lower serum chloride concentrations and enhanced upstream of RAAS pathway flux.

PMID:
42324236
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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