367 ALDOSTERONISM: A PROINFLAMMATORY PHENOTYPE SECONDARY TO CALCIUM OVERLOAD. (1st January 2005)

• Record Type: Journal Article
• Authors: Vidal, A.; Ahokas, R. A.; Sun, Y.; Bhattacharya, S. K.; Weber, K. T.
• Is Part Of: Journal of investigative medicine. Volume 53:Number 1(2005)
• Page Start: S318
• Page End: S318
• Publication Date: 2005-01-01
• Subjects: Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• DOI: 10.2310/6650.2005.00006.366
• Languages: English
• ISSNs: 1081-5589

Abstract

Abstract : Purpose: Aldosteronism, or inappropriate (relative to dietary Na+) elevations in plasma aldosterone (ALDO), such as occur in congestive heart failure (CHF), is accompanied by a proinflammatory phenotype involving diverse tissues, including immune cells and the heart. Herein we hypothesized that Ca2+ loading of these cells is the inducer and oxi/nitrosative stress the transducer of cell activation and which is mediated by elevations in parathyroid hormone (PTH) that appear due to the hypercalciuria and hypermagnesuria that accompany aldosteronism. Methods: Uninephrectomized rats received ALDO/salt treatment (ALDOST, 0.75 μg/h + dietary 1% NaCl/0.4% KCl) alone or in combination with either amlodipine, a Ca2+ channel blocker (CCB, 10 mg/day by gavage), or N-acetylcysteine, an antioxidant (NAC, 200 mg/kg qd ip). Age-/gender-matched, untreated animals served as controls. At 4 weeks treatment, we monitored cytosolic-free [Ca2+]i in peripheral blood mononuclear cells (PBMC); lymphocyte H2O2 production; 3-nitrotyrosine labeling in coronal sections of biventricular tissue; and plasma PTH. Results: At 4 weeks ALDOST and compared to controls, we found a rise in PBMC [Ca2+]i (76.4 ± 12.6 vs. 45.9 ± 2.4 nmol/L; p < .05); elevated lymphocyte H2O2 production (247.9 ± 17.7 vs. 96.8 ± 6.4 MCB; p < .05); an invasion of right and left ventricular tissue by inflammatory cells expressing 3-nitrotyrosine; and elevated plasma PTH (29.2 ± 7.44 vs. 10.9 ± 3.2 pmol/mL; p < .05). CCB and NAC each prevented PBMC Ca2+ loading and associated rise in H2O2 production and each attenuated the appearance of 3-nitrotyrosine-positive inflammatory cells in cardiac tissue. Conclusions: The proinflammatory phenotype that appears in aldosteronism is induced by Ca2+ loading of PBMC and is transduced by oxi/nitrosative stress. Secondary hyperparathyroidism is responsible for immune cell activation due to paradoxical intracellular Ca2+ loading, which can be prevented by reducing Ca2+ entry through channel blockade and/or antioxidant.