Causes and consequences of zinc dyshomeostasis in rats with chronic aldosteronism.
Causes and consequences of zinc dyshomeostasis in rats with chronic aldosteronism.
复制标题
DOI：
10.1097/fjc.0b013e3181833eb8
复制
发表时间：
2008-09
影响因子：
3
通讯作者：
Weber KT
中科院分区：
文献类型：
--
作者：
Gandhi MS;Deshmukh PA;Kamalov G;Zhao T;Zhao W;Whaley JT;Tichy JR;Bhattacharya SK;Ahokas RA;Sun Y;Gerling IC;Weber KT
Ca 2+和Mg 2+平衡的反复伴随醛固酮增多症（不适合饮食Na+摄入）。也会出现锌排泄增加和锌转运至受损组织，包括心脏。本研究探讨了醛固酮/盐治疗（ALDOST）大鼠锌稳态异常的原因和后果：1）尿酸化在促进高锌尿中的作用，乙酰唑胺（ACZ）在促进高锌尿中的作用，（75 mg/kg），一种碳酸酐酶抑制剂，被用作联合治疗，以提高尿HCO 3 −排泄; 2）评估心脏中的Zn水平，包括心肌细胞胞浆游离[Zn 2 +]i和线粒体Zn，金属硫蛋白（MT-1）（一种Zn结合蛋白）的表达，和氧化应激的生物标志物;和3）监测响应于ZnSO 4补充剂（40 mg/天）的氧化应激和心脏病理学。与对照组相比，ALDOST组4周时，我们发现：尿酸化和代谢紊乱与尿锌排泄增加和低锌血症相关，其中每一种都被乙酰唑胺预防：心脏锌升高，包括[Zn ~（2+）]i和线粒体锌升高，与组织MT-I、8-异前列腺素、丙二醛和gp 91 phox增加相关，与血浆和尿中的氧化应激相关; ZnSO 4可预防低锌血症，但不能预防离子性低钙血症，减轻氧化应激和显微镜下瘢痕形成，但不能预防壁内冠状动脉的血管炎和血管周围纤维化。因此，使用ALDOST时出现的高锌尿症是由于尿酸化所致。心脏中出现的氧化应激伴随着作为抗氧化剂的组织锌的增加。与硫酸锌共治疗减弱心肌细胞坏死，然而，可能需要多营养素补充剂来抵消伴随醛固酮增多症并导致心脏病理学的所有3种阳离子的动态平衡障碍。
Iterations in Ca2+ and Mg2+ balance accompany aldosteronism (inappropriate for dietary Na+ intake). Increased Zn excretion and Zn translocation to injured tissues, including the heart, also occurs. Several causes and consequences of Zn dyshomeostasis in rats receiving aldosterone/salt treatment (ALDOST) were examined: 1) the role of urinary acidification in promoting hyperzincuria, acetazolamide (75 mg/kg), a carbonic anhydrase inhibitor, was used as cotreatment to raise urinary HCO3− excretion; 2) assess Zn levels in the heart, including cardiomyocyte cytosolic free [Zn2+]i and mitochondrial Zn, the expression of metallothionein (MT-I), a Zn binding protein, and biomarkers of oxidative stress; and 3) monitor oxidative stress and cardiac pathology in response to ZnSO4 supplement (40 mg/day). Compared to controls, at 4 wks ALDOST we found: an acidification of urine and metabolic alkalosis associated with increased urinary Zn excretion and hypozincemia, each of which were prevented by acetazolamide; a rise in cardiac Zn including increased [Zn2+]i and mitochondrial Zn, associated with increased tissue MT-I, 8-isoprostane, malondialdehyde, and gp91phox, coupled with oxidative stress in plasma and urine; and ZnSO4 prevented hypozincemia, but not ionized hypocalcemia, and attenuated oxidative stress and microscopic scarring without preventing the vasculitis and perivascular fibrosis of intramural coronary arteries. Thus, the hyperzincuria seen with ALDOST is due to urinary acidification. The oxidative stress that appears in the heart is accompanied by increased tissue Zn serving as an antioxidant. Cotreatment with ZnSO4 attenuated cardiomyocyte necrosis, however, polynutrient supplement may be required to counteract the dyshomeostasis of all 3 cations that accompanies aldosteronism and contribute to cardiac pathology.