|Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats|
|Huang, Pan1; Chen, Siyao1; Wang, Yuan1; Liu, Jia1; Yao, Qiuyu1; Huang, Yaqian1; Li, Hongxia1; Zhu, Mingzhu1; Wang, Suxia2; Li, Lin3; Tang, Chaoshu4,5; Tao, Yinghong6; Yang, Guosheng6; Du, Junbao1,4; Jin, Hongfang1|
|关键词||Hydrogen sulfide Salt Hypertension Kidney|
|刊名||NITRIC OXIDE-BIOLOGY AND CHEMISTRY|
|WOS标题词||Science & Technology|
|类目[WOS]||Biochemistry & Molecular Biology ; Cell Biology|
|研究领域[WOS]||Biochemistry & Molecular Biology ; Cell Biology|
|关键词[WOS]||HYDROGEN-SULFIDE ; ANGIOTENSIN-II ; SENSITIVE HYPERTENSION ; BLOOD-PRESSURE ; DIETARY-SODIUM ; S RATS ; CELLS ; PATHOGENESIS ; GENERATION ; INHIBITION|
Background: The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats.
Methods: High-salt-induced hypertension rat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine beta-lyase (CBS), cystathionine gamma-Iyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1 alpha pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested.
Results: High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1 alpha was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1 alpha degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1 alpha activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt.
Conclusions: Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension. (C) 2015 Elsevier Inc. All rights reserved.
|项目编号||2012CB517806 ; 2013CB933801 ; 2011CB503904 ; 81370154 ; 81100181 ; 7121014 ; 7122184 ; 20130001120047 ; NCET-11-0005 ; 2014XXGB02|
|资助机构||Major Basic Research Development Program of People&prime ; s Republic of China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Grant of New Teachers, Doctoral Training Base of Ministry of Education, China ; Program for New Century Excellent Talents of Ministry of Education, China ; open project of Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education|
|作者单位||1.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China|
2.Peking Univ, Hosp 1, Cent Lab, Beijing 100034, Peoples R China
3.Minist Educ, Key Lab Mol Cardiol, Beijing 100191, Peoples R China
4.Peking Univ, Hosp 1, Anim Ctr, Beijing 100034, Peoples R China
5.Peking Univ, Hosp 1, Lab Elect Microscopy, Beijing 100034, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
|Huang, Pan,Chen, Siyao,Wang, Yuan,et al. Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats[J]. NITRIC OXIDE-BIOLOGY AND CHEMISTRY,2015,46(SI):192-203.|
|APA||Huang, Pan.,Chen, Siyao.,Wang, Yuan.,Liu, Jia.,Yao, Qiuyu.,...&Jin, Hongfang.(2015).Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats.NITRIC OXIDE-BIOLOGY AND CHEMISTRY,46(SI),192-203.|
|MLA||Huang, Pan,et al."Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats".NITRIC OXIDE-BIOLOGY AND CHEMISTRY 46.SI(2015):192-203.|