Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway
Background Irisin, as a myokine, plays a protective role against cardiovascular disease, including myocardial infarction, atherosclerosis and hypertension. However, whether irisin attenuates salt-sensitive hypertension and the related underlying mechanisms is unknown.Methods Male Dahl salt-resistant...
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Taylor & Francis Group
2024-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10641963.2024.2402258 |
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| author | Jie Mao Xiaocui Zhang Chunxiang Wang Suying Peng |
| author_facet | Jie Mao Xiaocui Zhang Chunxiang Wang Suying Peng |
| author_sort | Jie Mao |
| collection | DOAJ |
| description | Background Irisin, as a myokine, plays a protective role against cardiovascular disease, including myocardial infarction, atherosclerosis and hypertension. However, whether irisin attenuates salt-sensitive hypertension and the related underlying mechanisms is unknown.Methods Male Dahl salt-resistant (DSR) and Dahl salt-sensitive (DSS) (12 weeks) rats were fed a high salt diet (8% NaCl) with or without irisin treatment by intraperitoneal injection for 8 weeks.Results Compared with DSR rats, DSS rats showed higher systolic blood pressure (SBP), impaired natriuresis and diuresis and renal dysfunction. In addition, it was accompanied by downregulation of renal p-AMPKα and upregulation of renal RAC1 and nuclear mineralocorticoid receptor (MR). Irisin intervention could significantly up-regulated renal p-AMPKα level and down-regulated renal RAC1-MR signal, thereby improving renal sodium excretion and renal function, and ultimately reducing blood pressure in DSS rats. Ex vivo treatment with irisin reduced the expression of RAC1 and nuclear MR in primary renal distal convoluted tubule cells from DSS rats and the effects of irisin were abolished by cotreatment of compound C (AMPK inhibitor), indicating that the regulation of RAC1-MR signals by irisin depended on the activation of AMPK.Conclusions Irisin administration lowered salt-sensitive hypertension through regulating RAC1-MR signaling via activation of AMPK, which may be a promising therapeutic approach for salt-sensitive hypertension. |
| format | Article |
| id | doaj-art-5c9b33bc083f45dd87c9422b42df669b |
| institution | DOAJ |
| issn | 1064-1963 1525-6006 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Clinical and Experimental Hypertension |
| spelling | doaj-art-5c9b33bc083f45dd87c9422b42df669b2025-08-20T02:49:05ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062024-12-0146110.1080/10641963.2024.2402258Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathwayJie Mao0Xiaocui Zhang1Chunxiang Wang2Suying Peng3Department of Nephrology, Chongqing Fuling Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Nephrology, Chongqing Fuling Hospital, School of Medicine, Chongqing University, Chongqing, ChinaDepartment of Laboratory Animal Center, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Nephrology, Chongqing Fuling Hospital, School of Medicine, Chongqing University, Chongqing, ChinaBackground Irisin, as a myokine, plays a protective role against cardiovascular disease, including myocardial infarction, atherosclerosis and hypertension. However, whether irisin attenuates salt-sensitive hypertension and the related underlying mechanisms is unknown.Methods Male Dahl salt-resistant (DSR) and Dahl salt-sensitive (DSS) (12 weeks) rats were fed a high salt diet (8% NaCl) with or without irisin treatment by intraperitoneal injection for 8 weeks.Results Compared with DSR rats, DSS rats showed higher systolic blood pressure (SBP), impaired natriuresis and diuresis and renal dysfunction. In addition, it was accompanied by downregulation of renal p-AMPKα and upregulation of renal RAC1 and nuclear mineralocorticoid receptor (MR). Irisin intervention could significantly up-regulated renal p-AMPKα level and down-regulated renal RAC1-MR signal, thereby improving renal sodium excretion and renal function, and ultimately reducing blood pressure in DSS rats. Ex vivo treatment with irisin reduced the expression of RAC1 and nuclear MR in primary renal distal convoluted tubule cells from DSS rats and the effects of irisin were abolished by cotreatment of compound C (AMPK inhibitor), indicating that the regulation of RAC1-MR signals by irisin depended on the activation of AMPK.Conclusions Irisin administration lowered salt-sensitive hypertension through regulating RAC1-MR signaling via activation of AMPK, which may be a promising therapeutic approach for salt-sensitive hypertension.https://www.tandfonline.com/doi/10.1080/10641963.2024.2402258Irisinsalt-sensitive hypertensionRAC1aldosterone receptorAMPK |
| spellingShingle | Jie Mao Xiaocui Zhang Chunxiang Wang Suying Peng Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway Clinical and Experimental Hypertension Irisin salt-sensitive hypertension RAC1 aldosterone receptor AMPK |
| title | Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway |
| title_full | Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway |
| title_fullStr | Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway |
| title_full_unstemmed | Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway |
| title_short | Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway |
| title_sort | irisin mitigates salt sensitive hypertension via regulating renal ampk rac1 pathway |
| topic | Irisin salt-sensitive hypertension RAC1 aldosterone receptor AMPK |
| url | https://www.tandfonline.com/doi/10.1080/10641963.2024.2402258 |
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