Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-KB pathway

作者全名："Lei, Lifu; Zhang, Fuwei; Huang, Juan; Yang, Xinyue; Zhou, Xiaoxin; Yan, Hongjia; Chen, Caiyu; Zheng, Shuo; Si, Liangyi; Jose, Pedro A.; Zeng, Chunyu; Yang, Jian"

作者地址："[Lei, Lifu; Zhang, Fuwei; Huang, Juan; Zhou, Xiaoxin; Yan, Hongjia; Yang, Jian] Chongqing Med Univ, Res Ctr Metab & Cardiovasc Dis, Affiliated Hosp 3, Chongqing, Peoples R China; [Lei, Lifu; Huang, Juan; Zhou, Xiaoxin; Yan, Hongjia; Yang, Jian] Chongqing Med Univ, Dept Clin Nutr, Affiliated Hosp 3, Chongqing, Peoples R China; [Zhang, Fuwei; Si, Liangyi] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 3, Chongqing, Peoples R China; [Yang, Xinyue; Chen, Caiyu; Zheng, Shuo; Zeng, Chunyu] Third Mil Med Univ, Daping Hosp, Dept Cardiol, Chongqing, Peoples R China; [Yang, Xinyue; Chen, Caiyu; Zheng, Shuo; Zeng, Chunyu] Chongqing Inst Cardiol, Chongqing Cardiovasc Clin Res Ctr, Chongqing Key Lab Hypertens Res, Chongqing, Peoples R China; [Jose, Pedro A.] George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Sch Med & Hlth Sci, Washington, DC USA; [Jose, Pedro A.] George Washington Univ, Sch Med & Hlth Sci, Dept Physiol & Pharmacol, Washington, DC USA"

通信作者："Yang, J (通讯作者)，Chongqing Med Univ, Res Ctr Metab & Cardiovasc Dis, Affiliated Hosp 3, Chongqing, Peoples R China.; Zeng, CY (通讯作者)，Third Mil Med Univ, Daping Hosp, Dept Cardiol, Chongqing, Peoples R China."

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000955742500001

JCR分区：Q1

影响因子：7.4

年份：2023

卷号：200

期号：　

开始页：59

结束页：72

文献类型：Article

关键词：Angiotensin II type 1 receptor; Hypertension; Kidney; Oxidative stress; Selenium deficiency

摘要："Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT1R) expression and function that was reflected by the increase in sodium excretion after the intra-renal infusion of the AT1R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT1R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-KB p65 expression and activity, was involved in the regulation of renal AT1R expression because treatment with dithiocarbamate (PDTC), an NF-KB inhibitor, reversed the up-regulation of AT1R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT1R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT1R expression, Na+-K+-ATPase activity, hydrogen peroxide (H2O2) generation, and the nuclear translocation of NF-KB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H2O2 production by reducing GPx1 expression, which enhances NF-KB activity, increases renal AT1R expression, causes sodium retention and consequently increases blood pressure."

基金机构："National Natural Science Foundation of China [82070442, 81770425]; National Key R&D Program of China [2018YFC1312700]; Selenium Research Fund of Chongqing Nutrition Society [2019004]; Program of Chongqing Medical University for Youth Innovation in Future Medicine [W0085]; National Institutes of Health [P01HL074940, DK039308, DK119652]"

基金资助正文："This work was supported in part by grants from the National Natural Science Foundation of China (82070442, 81770425), National Key R&D Program of China (2018YFC1312700) , Selenium Research Fund of Chongqing Nutrition Society (2019004), Program of Chongqing Medical University for Youth Innovation in Future Medicine (W0085), and the National Institutes of Health (P01HL074940, DK039308, and DK119652)."