Abstract
We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory alterations in rat kidney by aldosterone + salt administration. The effects of treatment with spironolactone on above parameters were also analyzed. Male Wistar rats received aldosterone (1 mgkg-1d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg kg-1d-1). Systolic and diastolic blood pressures were elevated (p<0.05) in aldosterone + salt–treated rats. Relative kidney weight, collagen content, fibronectin, macrophage infiltrate, CTGF, Col I, MMP2, TNF-α, CD68, Arg2, and SGK-1 were increased (p<0.05) in aldosterone + salt–treated rats, being reduced by spironolactone (p<0.05). Increased iNOS and IFN-γ mRNA gene expression (M1 macrophage markers) was observed in aldosterone + salt rats, whereas no significant differences were observed in IL-10 and gene ArgI mRNA expression or ED2 protein content (M2 macrophage markers). All the observed changes were blocked with spironolactone treatment. Macrophage depletion with liposomal clodronate reduced macrophage influx and inflammatory M1 markers (INF-γ or iNOS), whereas interstitial fibrosis was only partially reduced after this intervention, in aldosterone plus salt-treated rats. In conclusion, aldosterone + salt administration mediates inflammatory M1 macrophage phenotype and increased fibrosis throughout mineralocorticoid receptors activation.
Highlights
Previous studies have demonstrated the importance of aldosterone in inflammatory and fibrotic processes development when related to kidney diseases [1]
We aimed to evaluate whether aldosterone+salt administration induces M1 polarization in rat kidney and whether mineralocorticoid receptors (MR) blockade prevent this pro-inflammatory macrophage subtype
The present study shows that administration of aldosterone plus salt in rats promotes a polarization towards a M1 phenotype by aldosterone, accompanied by hypertension, renal damage, hypertrophy and fibrosis
Summary
Previous studies have demonstrated the importance of aldosterone in inflammatory and fibrotic processes development when related to kidney diseases [1]. The effect of aldosterone on salt and water homeostasis and potassium excretion has been considered as its main renal. Desarrollo e Innovación Tecnológica de España (SAF2011-30396). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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