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Proinflammatory/profibrotic effects of aldosterone in Gitelman’s syndrome, a human model opposite to hypertension

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Abstract

Purpose

Aldosterone proinflammatory/profibrotic effects are mediated by the induction of mononuclear leucocytes (MNL) to express oxidative stress (OxSt)-related proteins, such as p22phox, and by the activation of RhoA/Rho kinase pathway. Gitelman’s syndrome (GS), an autosomal recessive tubulopathy, is an interesting opposite model to hypertension, being characterized by hypokalemia, activation of renin–angiotensin–aldosterone system yet normo/hypotension and lack of cardiovascular–renal remodeling. We aimed to evaluate the proinflammatory/profibrotic effect of aldosterone in MNL of 6 GS patients compared with 6 healthy subjects (HS).

Methods

p22phox expression and MYPT-1 phosphorylation status, a marker of RhoA/Rho kinase pathway activation, were evaluated in MNL of GS patients and HS at baseline and after incubation with aldosterone (1 × 10−8 M) alone or with canrenone (1 × 10−6 M).

Results

At basal condition, p22phox expression was significantly higher in HS than in GS patients (1.02 ± 0.05 densitometric unit (du) vs 0.40 ± 0.1 du, respectively). Aldosterone significantly increased p22phox expression in HS and this effect was reversed by coincubation with canrenone (1.4 ± 0.05 du and 1.09 ± 0.03 du, respectively). No significant change was reported in GS after incubation of MNL with aldosterone and/or canrenone compared with basaline. Even MYPT-1 phosphorylation was significantly higher in HS compared with GS patients at basal condition (1.16 ± 0.1 du vs 0.69 ± 0.07, respectively). Aldosterone significantly increased MYPT-1 phosphorylation only in HS (1.37 ± 0.1 du vs 0.83 ± 0.12 du in GS).

Conclusions

GS patients seem to be protected by the OxSt status induced by aldosterone and revealed in HS. This human model could provide additional clues to highlight the proinflammatory/cardiovascular remodeling effects of aldosterone.

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Authors and Affiliations

  1. Department of Medicine-Nephrology, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy

    V. Ravarotto, F. Simioni, E. Pagnin & L. A. Calò

  2. Department of Medicine-Endocrinology, University of Padova, Padua, Italy

    C. Sabbadin & D. Armanini

  3. Department of Medicine-Hypertension, University of Padova, Padua, Italy

    G. Maiolino

Authors
  1. V. Ravarotto
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  2. F. Simioni
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  3. C. Sabbadin
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  4. E. Pagnin
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  5. G. Maiolino
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  6. D. Armanini
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  7. L. A. Calò
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Correspondence to L. A. Calò.

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Ravarotto, V., Simioni, F., Sabbadin, C. et al. Proinflammatory/profibrotic effects of aldosterone in Gitelman’s syndrome, a human model opposite to hypertension. J Endocrinol Invest 42, 521–526 (2019). https://doi.org/10.1007/s40618-018-0942-9

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  • DOI: https://doi.org/10.1007/s40618-018-0942-9

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