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Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition

Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both sa...

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Autores principales: Huang, Pan, Huang, Yaqian, Lv, Boyang, Zhang, Heng, Liu, Jia, Yang, Guosheng, Tao, Yinghong, Bu, Dingfang, Wang, Guang, Du, Junbao, Jin, Hongfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413057/
https://www.ncbi.nlm.nih.gov/pubmed/34484563
http://dx.doi.org/10.1155/2021/5530907
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author Huang, Pan
Huang, Yaqian
Lv, Boyang
Zhang, Heng
Liu, Jia
Yang, Guosheng
Tao, Yinghong
Bu, Dingfang
Wang, Guang
Du, Junbao
Jin, Hongfang
author_facet Huang, Pan
Huang, Yaqian
Lv, Boyang
Zhang, Heng
Liu, Jia
Yang, Guosheng
Tao, Yinghong
Bu, Dingfang
Wang, Guang
Du, Junbao
Jin, Hongfang
author_sort Huang, Pan
collection PubMed
description Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal H(2)S content and enhanced cystathionine-β-synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited H(2)S generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/H(2)S pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats.
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spelling pubmed-84130572021-09-03 Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition Huang, Pan Huang, Yaqian Lv, Boyang Zhang, Heng Liu, Jia Yang, Guosheng Tao, Yinghong Bu, Dingfang Wang, Guang Du, Junbao Jin, Hongfang Oxid Med Cell Longev Research Article Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal H(2)S content and enhanced cystathionine-β-synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited H(2)S generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/H(2)S pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats. Hindawi 2021-08-25 /pmc/articles/PMC8413057/ /pubmed/34484563 http://dx.doi.org/10.1155/2021/5530907 Text en Copyright © 2021 Pan Huang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Pan
Huang, Yaqian
Lv, Boyang
Zhang, Heng
Liu, Jia
Yang, Guosheng
Tao, Yinghong
Bu, Dingfang
Wang, Guang
Du, Junbao
Jin, Hongfang
Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition
title Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition
title_full Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition
title_fullStr Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition
title_full_unstemmed Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition
title_short Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H(2)S Inhibition
title_sort endogenous taurine downregulation is required for renal injury in salt-sensitive hypertensive rats via cbs/h(2)s inhibition
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413057/
https://www.ncbi.nlm.nih.gov/pubmed/34484563
http://dx.doi.org/10.1155/2021/5530907
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