Responses in extracellular and intracellular calcium and magnesium in aldosteronism

Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, Tennessee 38136, USA.
Journal of Laboratory and Clinical Medicine (Impact Factor: 2.8). 09/2005; 146(2):76-84. DOI: 10.1016/j.lab.2005.04.008
Source: PubMed


We hypothesized the hypercalciuria and hypermagnesuria that accompany aldosteronism could be pharmacologically attenuated to prevent shifts in extracellular and intracellular levels of these divalent cations and the adverse outcomes associated with them. Accordingly, rats administered aldosterone/salt treatment (ALDOST) were cotreated with either hydrochlorothiazide (Hctz), to selectively reabsorb urinary Ca2+, or with Hctz plus spironolactone (Hctz+Spi), where Spi retards the excretion of these cations in both urine and feces. We monitored urinary excretion and responses in extracellular and intracellular Ca2+ and Mg2+, together with indices of oxi/nitrosative stress in plasma and ventricular tissue. At 4 weeks ALDOST we found the following: (1) hypercalciuria was reduced by Hctz and normalized by Hctz+Spi, and this combination, unlike Hctz alone, also rescued hypermagnesuria; (2) the decrease in plasma-ionized [Ca2+]o was not seen with Hctz or Hctz+Spi, whereas Spi cotreatment protected against a decline in [Mg2+]o; (3) the Ca2+ loading of peripheral blood mononuclear cells and cardiac tissue was not seen with Hctz+Spi; and (4) the induction of oxi/nitrosative stress, expressed as reduced plasma alpha1-antiproteinase activity and activation of gp91(phox) subunit of NADPH oxidase in inflammatory cells invading intramural coronary arteries of the right and left ventricles, together with vascular fibrosis, was completely prevented by Spi cotreatment. In rats with aldosteronism, cotreatment with Hctz+Spi more effectively (vis-à-vis Hctz alone) protects against adverse iterations in extracellular and intracellular concentrations of Ca2+ and Mg2+, as well as the appearance of oxi/nitrosative stress to prevent the proinflammatory vascular phenotype.

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Available from: Karl T Weber, Jul 28, 2015
    • "This finding is in line with the effect of lithium on erythrocyte Mg 2þ , which shows acutely an increase, but no change in the long term, pointing to the importance of adaptive changes (Dunner et al., 1975). Compounds with properties to increase intracellular Mg 2þ express antidepressive efficacy in preliminary animal experiments or preliminary clinical trials: These are for example mineralocorticoid receptor antagonists (Ahokas et al., 2003; Runyan et al., 2005); which protect against aldosterone induced Mg 2þ depletion and by this mechanism may have an antidepressant effect (Ebel et al., 1971; Hlavacova et al., 2011; Murck et al., 2012). Antidiabetic drugs of the glitazone group lead to an increase of Mg 2þ in peripheral mononuclear cells in vitro (Alon et al., 2006) and have antidepressant effects in animal models (Salehi-Sadaghiani et al., 2012) and in clinical trials (Rasgon et al., 2010; Sepanjnia et al., Author's personal copy 2012). "
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