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 [Ca2+]o and [Mg2+]o, parathyroid hormone and 1-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 [Ca2+]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 Ca2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma 1-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 [Mg2+]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.
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 [Ca2+]o and [Mg2+]o, parathyroid hormone and 1-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 [Ca2+]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 Ca2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma 1-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 [Mg2+]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.
Authors: Atta U Shahbaz; Tieqiang Zhao; Wenyuan Zhao; Patti L Johnson; Robert A Ahokas; Syamal K Bhattacharya; Yao Sun; Ivan C Gerling; Karl T Weber Journal: Am J Physiol Heart Circ Physiol Date: 2010-11-12 Impact factor: 4.733
Authors: Malay S Gandhi; Prajwal A Deshmukh; German Kamalov; Tieqiang Zhao; Wenyuan Zhao; Jonathan T Whaley; Jill R Tichy; Syamal K Bhattacharya; Robert A Ahokas; Yao Sun; Ivan C Gerling; Karl T Weber Journal: J Cardiovasc Pharmacol Date: 2008-09 Impact factor: 3.105
Authors: G Loncar; B Bozic; N Cvetinovic; H-D Dungen; M Lainscak; S von Haehling; W Doehner; Z Radojicic; B Putnikovic; T Trippel; V Popovic Journal: J Endocrinol Invest Date: 2016-10-13 Impact factor: 4.256
Authors: Barbara Altieri; Giovanna Muscogiuri; Stavroula A Paschou; Andromachi Vryonidou; Silvia Della Casa; Alfredo Pontecorvi; Martin Fassnacht; Cristina L Ronchi; John Newell-Price Journal: Endocrine Date: 2018-08-02 Impact factor: 3.633
Authors: German Kamalov; Robert A Ahokas; Wenyuan Zhao; Tieqiang Zhao; Atta U Shahbaz; Patti L Johnson; Syamal K Bhattacharya; Yao Sun; Ivan C Gerling; Karl T Weber Journal: J Cardiovasc Pharmacol Date: 2010-03 Impact factor: 3.105