Goodwin Kayla D, Sun Yao, Weber Karl T, Bhattacharya Syamal K, Ahokas Robert A, Gerling Ivan C
Division of Cardiovascular Diseases, University of Tennessee Health Science Center Memphis, Tennessee.
Division of Cardiovascular Diseases, University of Tennessee Health Science Center Memphis, Tennessee..
Am J Med Sci. 2006 Aug;332(2):73-78. doi: 10.1097/00000441-200608000-00004.
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).
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.
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.
充血性心力衰竭（CHF）临床综合征的显著特征包括醛固酮增多症和氧化应激的存在。继发性甲状旁腺功能亢进（SHPT）因钙的尿排泄和粪排泄增加而伴随醛固酮增多症。SHPT导致包括外周血单核细胞（PBMC）在内的多种细胞的细胞内钙超载以及氧化应激的出现。甲状旁腺切除术或钙通道阻滞剂均可预防这些反应。在此，我们假设骨化三醇或1,25(OH)2D3加上补充钙和镁的饮食（CMD）可预防接受醛固酮/盐处理（ALDOST）的大鼠发生SHPT以及PBMC的钙超载，从而预防这些细胞中的氧化应激。
在接受ALDOST 4周的大鼠中，无论有无CMD，我们监测了血浆离子钙[Ca]o和甲状旁腺激素（PTH），以及PBMC胞质游离钙[Ca]i和过氧化氢（H2O2）的产生。未接受处理、年龄和性别匹配的大鼠作为对照。与对照组相比，ALDOST导致血浆[Ca]o水平预期下降，同时血浆PTH水平升高，PBMC细胞内钙超载以及其H2O2产生增加。CMD预防了SHPT，消除了PBMC的细胞内钙超载及其H2O2产生增加。
血浆[Ca]o下降诱导的醛固酮增多症中SHPT的出现导致PTH介导的PBMC钙超载及其H2O2产生增加。骨化三醇和补充钙和镁的饮食可预防醛固酮增多症大鼠的SHPT。这些发现提出了CHF中发现的SHPT可用大量营养素和微量营养素进行管理的前景。
