Aldosteronism and peripheral blood mononuclear cell activation

a neuroendocrine-immune interface.

Robert A. Ahokas, Kenneth J Warrington, Ivan C. Gerling, Yao Sun, Linus A. Wodi, Paula A. Herring, L. Lu, Syamal K. Bhattacharya, Arnold E. Postlethwaite, Karl T. Weber

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of the heart and systemic organs. It remains uncertain whether peripheral blood mononuclear cells (PBMCs) are activated before tissue invasion by monocytes/macrophages and lymphocytes, as is the case for responsible pathogenic mechanisms. Uninephrectomized rats treated for 4 weeks with dietary 1% NaCl and aldosterone (ALDOST, 0.75 microg/h) with or without spironolactone (Spi, 100 mg/kg per daily gavage) were compared with unoperated/untreated and uninephrectomized/salt-treated controls. Before intramural coronary vascular lesions appeared at week 4 of ALDOST, we found (1) a reduction of PBMC cytosolic free [Mg2+]i, together with intracellular Mg2+ and Ca2+ loading, whereas plasma and cardiac tissue Mg2+ were no different from controls; (2) increased H2O2 production by monocytes and lymphocytes together with upregulated PBMC gene expression of oxidative stress-inducible tyrosine phosphatase and Mn2+-superoxide dismutase and the presence of 3-nitrotyrosine in CD4+ and ED-1-positive inflammatory cells that had invaded intramural coronary arteries; (3) B-cell activation, including transcription of immunoglobulins, intracellular adhesion molecule-1, and CC and CXC chemokines and their receptors; (4) expansion of B lymphocyte subset and myosin heavy chain class II-expressing lymphocytes; and (5) autoreactivity with gene expression for antibodies to acetylcholine receptors and a downregulation of RT-6.2, which is in keeping with cell activation and associated with autoimmunity. Spi cotreatment attenuated the rise in intracellular Ca2+, the appearance of oxidative/nitrosative stress in PBMCs and invading inflammatory cells, and alterations in PBMC transcriptome. Thus, aldosteronism is associated with an activation of circulating immune cells induced by iterations in PBMC divalent cations and transduced by oxidative/nitrosative stress. ALDO receptor antagonism modulates this neuroendocrine-immune interface. The full text of this article is available online at http://www.circresaha.org.

Original languageEnglish (US)
JournalCirculation Research
Volume93
Issue number10
StatePublished - Nov 14 2003
Externally publishedYes

Fingerprint

Hyperaldosteronism
Blood Cells
Oxidative Stress
Lymphocytes
Blood Vessels
Monocytes
CXCR Receptors
B-Lymphocyte Subsets
Gene Expression
CC Chemokines
Spironolactone
Myosin Heavy Chains
Divalent Cations
Cholinergic Receptors
Aldosterone
Autoimmunity
Transcriptome
Phosphoric Monoester Hydrolases
Transcriptional Activation
Superoxide Dismutase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ahokas, R. A., Warrington, K. J., Gerling, I. C., Sun, Y., Wodi, L. A., Herring, P. A., ... Weber, K. T. (2003). Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. Circulation Research, 93(10).

Aldosteronism and peripheral blood mononuclear cell activation : a neuroendocrine-immune interface. / Ahokas, Robert A.; Warrington, Kenneth J; Gerling, Ivan C.; Sun, Yao; Wodi, Linus A.; Herring, Paula A.; Lu, L.; Bhattacharya, Syamal K.; Postlethwaite, Arnold E.; Weber, Karl T.

In: Circulation Research, Vol. 93, No. 10, 14.11.2003.

Research output: Contribution to journalArticle

Ahokas, RA, Warrington, KJ, Gerling, IC, Sun, Y, Wodi, LA, Herring, PA, Lu, L, Bhattacharya, SK, Postlethwaite, AE & Weber, KT 2003, 'Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface.', Circulation Research, vol. 93, no. 10.
Ahokas, Robert A. ; Warrington, Kenneth J ; Gerling, Ivan C. ; Sun, Yao ; Wodi, Linus A. ; Herring, Paula A. ; Lu, L. ; Bhattacharya, Syamal K. ; Postlethwaite, Arnold E. ; Weber, Karl T. / Aldosteronism and peripheral blood mononuclear cell activation : a neuroendocrine-immune interface. In: Circulation Research. 2003 ; Vol. 93, No. 10.
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abstract = "Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of the heart and systemic organs. It remains uncertain whether peripheral blood mononuclear cells (PBMCs) are activated before tissue invasion by monocytes/macrophages and lymphocytes, as is the case for responsible pathogenic mechanisms. Uninephrectomized rats treated for 4 weeks with dietary 1{\%} NaCl and aldosterone (ALDOST, 0.75 microg/h) with or without spironolactone (Spi, 100 mg/kg per daily gavage) were compared with unoperated/untreated and uninephrectomized/salt-treated controls. Before intramural coronary vascular lesions appeared at week 4 of ALDOST, we found (1) a reduction of PBMC cytosolic free [Mg2+]i, together with intracellular Mg2+ and Ca2+ loading, whereas plasma and cardiac tissue Mg2+ were no different from controls; (2) increased H2O2 production by monocytes and lymphocytes together with upregulated PBMC gene expression of oxidative stress-inducible tyrosine phosphatase and Mn2+-superoxide dismutase and the presence of 3-nitrotyrosine in CD4+ and ED-1-positive inflammatory cells that had invaded intramural coronary arteries; (3) B-cell activation, including transcription of immunoglobulins, intracellular adhesion molecule-1, and CC and CXC chemokines and their receptors; (4) expansion of B lymphocyte subset and myosin heavy chain class II-expressing lymphocytes; and (5) autoreactivity with gene expression for antibodies to acetylcholine receptors and a downregulation of RT-6.2, which is in keeping with cell activation and associated with autoimmunity. Spi cotreatment attenuated the rise in intracellular Ca2+, the appearance of oxidative/nitrosative stress in PBMCs and invading inflammatory cells, and alterations in PBMC transcriptome. Thus, aldosteronism is associated with an activation of circulating immune cells induced by iterations in PBMC divalent cations and transduced by oxidative/nitrosative stress. ALDO receptor antagonism modulates this neuroendocrine-immune interface. The full text of this article is available online at http://www.circresaha.org.",
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AU - Gerling, Ivan C.

AU - Sun, Yao

AU - Wodi, Linus A.

AU - Herring, Paula A.

AU - Lu, L.

AU - Bhattacharya, Syamal K.

AU - Postlethwaite, Arnold E.

AU - Weber, Karl T.

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