Preventing oxidative stress in rats with aldosteronism by calcitriol and dietary calcium and magnesium supplements.
BACKGROUND
Prominent features of the clinical syndrome of congestive heart failure (CHF) include aldosteronism and the presence of oxidative stress. Secondary hyperparathyroidism (SHPT) accompanies aldosteronism due to increased urinary and fecal excretion of Ca. SHPT accounts for intracellular Ca overloading of diverse cells, including peripheral blood mononuclear cells (PBMC), and the appearance of oxidative stress. Parathyroidectomy or a Ca channel blocker each prevent these responses. Herein, we hypothesized calcitriol, or 1,25(OH)2D3, plus a diet supplemented with Ca and Mg (CMD) would prevent SHPT and Ca overloading of PBMC and thereby oxidative stress in these cells in rats receiving aldosterone/salt treatment (ALDOST).


RESULTS
In rats with ALDOST for 4 weeks, without or with CMD, we monitored plasma-ionized [Ca]o and parathyroid hormone (PTH), and PBMC cytosolic-free [Ca]i and H2O2 production. Untreated, age- and gender-matched rats served as controls. Compared to controls, ALDOST led to an expected fall in plasma [Ca]o level with accompanying rise in plasma PTH level and intracellular Ca overloading of PBMC and their increased production of H2O2. CMD prevented SHPT and abrogated intracellular Ca overloading of PBMC and their increased H2O2 production.


CONCLUSIONS
The appearance of SHPT in aldosteronism, induced by fallen plasma [Ca]o, leads to PTH-mediated Ca overloading of PBMC and their increased production of H2O2. SHPT in rats with aldosteronism can be prevented by calcitriol and a diet supplemented with Ca and Mg. These findings raise the prospect that the SHPT found in CHF could be managed with macro- and micronutrients.
Goodwin
Kayla D
KD
Division of Cardiovascular Diseases, University of Tennessee Health Science Center Memphis, Tennessee.
Sun
Yao
Y
Division of Cardiovascular Diseases, University of Tennessee Health Science Center Memphis, Tennessee.
Weber
Karl T
KT
Division of Cardiovascular Diseases, University of Tennessee Health Science Center Memphis, Tennessee.. Electronic address: KTWeber@utmem.edu.
Bhattacharya
Syamal K
SK
Division of Cardiovascular Diseases, Department of Surgery, University of Tennessee Health Science Center Memphis, Tennessee.
Ahokas
Robert A
RA
Department of Obstetrics & Gynecology, University of Tennessee Health Science Center Memphis, Tennessee.
Gerling
Ivan C
IC
Division of Endocrinology, University of Tennessee Health Science Center Memphis, Tennessee.
D000450:Aldosterone / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D003593:Cytoplasm / Q000378:metabolism; D019587:Dietary Supplements; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000178:diet therapy / Q000652:urine; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006929:Hyperaldosteronism / Q000097:blood / Q000139:chemically induced / Q000178:diet therapy* / Q000652:urine; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology / Q000517:prevention & control / Q000652:urine; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008274:Magnesium / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D010281:Parathyroid Hormone; D000450:Aldosterone; D006861:Hydrogen Peroxide; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium