Abstract

Background - Aldosteronism may account for oxi/nitrosative stress, a proinflammatory phenotype, and wasting in congestive heart failure. We hypothesized that aldosterone/1% NaCl treatment (ALDOST) in rats enhances Ca2+ and Mg2+ excretion and leads to systemic effects, including bone loss. Methods and Results - At 1, 2, 4, and 6 weeks of ALDOST, we monitored Ca2+ and Mg2+ excretion, ionized [Ca 2+]o and [Mg2+]o, parathyroid hormone and α1-antiproteinase activity in plasma, bone mineral density, bone strength, Ca2+ and Mg2+ content in peripheral blood mononuclear cells (PBMCs) and ventricular tissue, and lymphocyte H2O2 production. A separate group received spironolactone (Spiro), an aldosterone receptor antagonist. Age- and gender-matched unoperated and untreated rats served as controls. ALDOST induced a marked (P<0.05) and persistent rise in urinary and fecal Ca2+ and Mg2+ excretion, a progressive reduction (P<0.05) in [Ca 2+]o and [Mg2+]o, and an elevation in parathyroid hormone (P<0.05) with a fall (P<0.05) in bone mineral density and strength. An early, sustained increase (P<0.05) in PBMC Ca 2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma α1-antiproteinase activity was reduced (P<0.05), whereas lymphocyte H2O2 production was increased (P<0.05) at all time points. Spiro cotreatment attenuated (P<0.05) urinary and fecal Ca2+ and Mg2+ excretion, prevented the fall in [Ca2+]o and [Mg 2+]o, rescued bone mineral density and strength, and prevented Ca2+ overloading of PBMCs and cardiomyocytes. Conclusions - In aldosteronism, Ca2+ and Mg2+ losses lead to a fall in [Ca2+]o and [Mg2+]o with secondary hyperparathyroidism and bone resorption. Ca2+ overloading of PBMCs and cardiac tissue leads to oxi/nitrosative stress and a proinflammatory phenotype.

Original languageEnglish (US)
Pages (from-to)871-878
Number of pages8
JournalCirculation
Volume111
Issue number7
DOIs
StatePublished - Feb 22 2005

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Hyperaldosteronism
Hyperparathyroidism
Blood Cells
Aldosterone
Bone Density
Calcium
Parathyroid Hormone
Lymphocytes
Mineralocorticoid Receptor Antagonists
Phenotype
Bone and Bones
Spironolactone
Secondary Hyperparathyroidism
Bone Resorption
Cardiac Myocytes
Heart Failure
Formoterol Fumarate

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Hyperparathyroidism and the calcium paradox of aldosteronism. / Chhokar, Vikram S.; Sun, Yao; Bhattacharya, Syamal; Ahokas, Robert A.; Myers, Linda; Xing, Zhiqing; Smith, Richard; Gerling, Ivan; Weber, Karl.

In: Circulation, Vol. 111, No. 7, 22.02.2005, p. 871-878.

Research output: Contribution to journalArticle

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title = "Hyperparathyroidism and the calcium paradox of aldosteronism",
abstract = "Background - Aldosteronism may account for oxi/nitrosative stress, a proinflammatory phenotype, and wasting in congestive heart failure. We hypothesized that aldosterone/1{\%} NaCl treatment (ALDOST) in rats enhances Ca2+ and Mg2+ excretion and leads to systemic effects, including bone loss. Methods and Results - At 1, 2, 4, and 6 weeks of ALDOST, we monitored Ca2+ and Mg2+ excretion, ionized [Ca 2+]o and [Mg2+]o, parathyroid hormone and α1-antiproteinase activity in plasma, bone mineral density, bone strength, Ca2+ and Mg2+ content in peripheral blood mononuclear cells (PBMCs) and ventricular tissue, and lymphocyte H2O2 production. A separate group received spironolactone (Spiro), an aldosterone receptor antagonist. Age- and gender-matched unoperated and untreated rats served as controls. ALDOST induced a marked (P<0.05) and persistent rise in urinary and fecal Ca2+ and Mg2+ excretion, a progressive reduction (P<0.05) in [Ca 2+]o and [Mg2+]o, and an elevation in parathyroid hormone (P<0.05) with a fall (P<0.05) in bone mineral density and strength. An early, sustained increase (P<0.05) in PBMC Ca 2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma α1-antiproteinase activity was reduced (P<0.05), whereas lymphocyte H2O2 production was increased (P<0.05) at all time points. Spiro cotreatment attenuated (P<0.05) urinary and fecal Ca2+ and Mg2+ excretion, prevented the fall in [Ca2+]o and [Mg 2+]o, rescued bone mineral density and strength, and prevented Ca2+ overloading of PBMCs and cardiomyocytes. Conclusions - In aldosteronism, Ca2+ and Mg2+ losses lead to a fall in [Ca2+]o and [Mg2+]o with secondary hyperparathyroidism and bone resorption. Ca2+ overloading of PBMCs and cardiac tissue leads to oxi/nitrosative stress and a proinflammatory phenotype.",
author = "Chhokar, {Vikram S.} and Yao Sun and Syamal Bhattacharya and Ahokas, {Robert A.} and Linda Myers and Zhiqing Xing and Richard Smith and Ivan Gerling and Karl Weber",
year = "2005",
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T1 - Hyperparathyroidism and the calcium paradox of aldosteronism

AU - Chhokar, Vikram S.

AU - Sun, Yao

AU - Bhattacharya, Syamal

AU - Ahokas, Robert A.

AU - Myers, Linda

AU - Xing, Zhiqing

AU - Smith, Richard

AU - Gerling, Ivan

AU - Weber, Karl

PY - 2005/2/22

Y1 - 2005/2/22

N2 - Background - Aldosteronism may account for oxi/nitrosative stress, a proinflammatory phenotype, and wasting in congestive heart failure. We hypothesized that aldosterone/1% NaCl treatment (ALDOST) in rats enhances Ca2+ and Mg2+ excretion and leads to systemic effects, including bone loss. Methods and Results - At 1, 2, 4, and 6 weeks of ALDOST, we monitored Ca2+ and Mg2+ excretion, ionized [Ca 2+]o and [Mg2+]o, parathyroid hormone and α1-antiproteinase activity in plasma, bone mineral density, bone strength, Ca2+ and Mg2+ content in peripheral blood mononuclear cells (PBMCs) and ventricular tissue, and lymphocyte H2O2 production. A separate group received spironolactone (Spiro), an aldosterone receptor antagonist. Age- and gender-matched unoperated and untreated rats served as controls. ALDOST induced a marked (P<0.05) and persistent rise in urinary and fecal Ca2+ and Mg2+ excretion, a progressive reduction (P<0.05) in [Ca 2+]o and [Mg2+]o, and an elevation in parathyroid hormone (P<0.05) with a fall (P<0.05) in bone mineral density and strength. An early, sustained increase (P<0.05) in PBMC Ca 2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma α1-antiproteinase activity was reduced (P<0.05), whereas lymphocyte H2O2 production was increased (P<0.05) at all time points. Spiro cotreatment attenuated (P<0.05) urinary and fecal Ca2+ and Mg2+ excretion, prevented the fall in [Ca2+]o and [Mg 2+]o, rescued bone mineral density and strength, and prevented Ca2+ overloading of PBMCs and cardiomyocytes. Conclusions - In aldosteronism, Ca2+ and Mg2+ losses lead to a fall in [Ca2+]o and [Mg2+]o with secondary hyperparathyroidism and bone resorption. Ca2+ overloading of PBMCs and cardiac tissue leads to oxi/nitrosative stress and a proinflammatory phenotype.

AB - Background - Aldosteronism may account for oxi/nitrosative stress, a proinflammatory phenotype, and wasting in congestive heart failure. We hypothesized that aldosterone/1% NaCl treatment (ALDOST) in rats enhances Ca2+ and Mg2+ excretion and leads to systemic effects, including bone loss. Methods and Results - At 1, 2, 4, and 6 weeks of ALDOST, we monitored Ca2+ and Mg2+ excretion, ionized [Ca 2+]o and [Mg2+]o, parathyroid hormone and α1-antiproteinase activity in plasma, bone mineral density, bone strength, Ca2+ and Mg2+ content in peripheral blood mononuclear cells (PBMCs) and ventricular tissue, and lymphocyte H2O2 production. A separate group received spironolactone (Spiro), an aldosterone receptor antagonist. Age- and gender-matched unoperated and untreated rats served as controls. ALDOST induced a marked (P<0.05) and persistent rise in urinary and fecal Ca2+ and Mg2+ excretion, a progressive reduction (P<0.05) in [Ca 2+]o and [Mg2+]o, and an elevation in parathyroid hormone (P<0.05) with a fall (P<0.05) in bone mineral density and strength. An early, sustained increase (P<0.05) in PBMC Ca 2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma α1-antiproteinase activity was reduced (P<0.05), whereas lymphocyte H2O2 production was increased (P<0.05) at all time points. Spiro cotreatment attenuated (P<0.05) urinary and fecal Ca2+ and Mg2+ excretion, prevented the fall in [Ca2+]o and [Mg 2+]o, rescued bone mineral density and strength, and prevented Ca2+ overloading of PBMCs and cardiomyocytes. Conclusions - In aldosteronism, Ca2+ and Mg2+ losses lead to a fall in [Ca2+]o and [Mg2+]o with secondary hyperparathyroidism and bone resorption. Ca2+ overloading of PBMCs and cardiac tissue leads to oxi/nitrosative stress and a proinflammatory phenotype.

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