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

PurposeAldosterone proinflammatory/profibrotic effects are mediated by the induction of mononuclear leucocytes (MNL) to express oxidative stress (OxSt)-related proteins, such as p22(phox), 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).Methodsp22(phox) 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 (1x10(-8)M) alone or with canrenone (1x10(-6)M).ResultsAt basal condition, p22(phox) expression was significantly higher in HS than in GS patients (1.020.05densitometric unit (du) vs 0.40 +/- 0.1du, respectively). Aldosterone significantly increased p22(phox) expression in HS and this effect was reversed by coincubation with canrenone (1.4 +/- 0.05du and 1.09 +/- 0.03du, 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 +/- 0.1du vs 0.69 +/- 0.07, respectively). Aldosterone significantly increased MYPT-1 phosphorylation only in HS (1.37 +/- 0.1du vs 0.83 +/- 0.12du in GS).Conclusions p id=Par4 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.