Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats
Background Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of hypertension. However, the underlying mechanisms for lowering blood pressure (BP) by suppressing ER stress remain unclear. Here, we hypothesized that inhibition of ER stress could restore the b...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | http://dx.doi.org/10.1080/10641963.2023.2202367 |
| _version_ | 1797681069161447424 |
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| author | Jun Zhu Anjing Shao Chunyan Wang Chensi Zeng Hongyong Wang |
| author_facet | Jun Zhu Anjing Shao Chunyan Wang Chensi Zeng Hongyong Wang |
| author_sort | Jun Zhu |
| collection | DOAJ |
| description | Background Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of hypertension. However, the underlying mechanisms for lowering blood pressure (BP) by suppressing ER stress remain unclear. Here, we hypothesized that inhibition of ER stress could restore the balance between RAS components and lower BP in spontaneously hypertensive rats (SHRs). Methods Wistar-Kyoto (WKY) rats and SHRs received vehicle or 4-PBA, an ER stress inhibitor, in the drinking water for 4 weeks. BP was measured by tail-cuff plethysmography, and the expression of RAS components was examined by Western blot. Results Compared with vehicle-treated WKY rats, vehicle-treated SHRs exhibited higher blood pressure and increased renal ER stress and oxidative stress, accompanied by impaired diuresis and natriuresis. Moreover, SHRs had higher ACE and AT1R and lower AT2R, ACE2, and MasR expressions in the kidney. Interestingly, 4-PBA treatment improved impaired diuresis and natriuresis and lowered blood pressure in SHRs, accompanied by reducing ACE and AT1R protein expression and increasing AT2R, ACE2, and MasR expression in the kidneys of SHRs. In addition, these changes were associated with the reduction of ER stress and oxidative stress. Conclusions These results suggest that the imbalance of renal RAS components was associated with increased ER stress in SHRs. Inhibition of ER stress with 4-PBA reversed the imbalance of renal RAS components and restored the impaired diuresis and natriuresis, which, at least in part, explains the blood pressure-lowering effects of 4-PBA in hypertension. |
| first_indexed | 2024-03-11T23:39:38Z |
| format | Article |
| id | doaj.art-16323f4ad7cf4662a61bb0cba991cf64 |
| institution | Directory Open Access Journal |
| issn | 1064-1963 1525-6006 |
| language | English |
| last_indexed | 2024-03-11T23:39:38Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Clinical and Experimental Hypertension |
| spelling | doaj.art-16323f4ad7cf4662a61bb0cba991cf642023-09-19T16:04:08ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062023-12-0145110.1080/10641963.2023.22023672202367Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive ratsJun Zhu0Anjing Shao1Chunyan Wang2Chensi Zeng3Hongyong Wang4The Third Military Medical University (Army Medical University)The Third Military Medical University (Army Medical University)Third People’s Hospital, Kaizhou DistrictChongqing Cancer HospitalThe Third Military Medical University (Army Medical University)Background Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of hypertension. However, the underlying mechanisms for lowering blood pressure (BP) by suppressing ER stress remain unclear. Here, we hypothesized that inhibition of ER stress could restore the balance between RAS components and lower BP in spontaneously hypertensive rats (SHRs). Methods Wistar-Kyoto (WKY) rats and SHRs received vehicle or 4-PBA, an ER stress inhibitor, in the drinking water for 4 weeks. BP was measured by tail-cuff plethysmography, and the expression of RAS components was examined by Western blot. Results Compared with vehicle-treated WKY rats, vehicle-treated SHRs exhibited higher blood pressure and increased renal ER stress and oxidative stress, accompanied by impaired diuresis and natriuresis. Moreover, SHRs had higher ACE and AT1R and lower AT2R, ACE2, and MasR expressions in the kidney. Interestingly, 4-PBA treatment improved impaired diuresis and natriuresis and lowered blood pressure in SHRs, accompanied by reducing ACE and AT1R protein expression and increasing AT2R, ACE2, and MasR expression in the kidneys of SHRs. In addition, these changes were associated with the reduction of ER stress and oxidative stress. Conclusions These results suggest that the imbalance of renal RAS components was associated with increased ER stress in SHRs. Inhibition of ER stress with 4-PBA reversed the imbalance of renal RAS components and restored the impaired diuresis and natriuresis, which, at least in part, explains the blood pressure-lowering effects of 4-PBA in hypertension.http://dx.doi.org/10.1080/10641963.2023.2202367endoplasmic reticulum stresshypertensionrenin-angiotensin systemoxidative stresskidney |
| spellingShingle | Jun Zhu Anjing Shao Chunyan Wang Chensi Zeng Hongyong Wang Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats Clinical and Experimental Hypertension endoplasmic reticulum stress hypertension renin-angiotensin system oxidative stress kidney |
| title | Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats |
| title_full | Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats |
| title_fullStr | Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats |
| title_full_unstemmed | Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats |
| title_short | Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats |
| title_sort | inhibition of endoplasmic reticulum stress restores the balance of renal ras components and lowers blood pressure in the spontaneously hypertensive rats |
| topic | endoplasmic reticulum stress hypertension renin-angiotensin system oxidative stress kidney |
| url | http://dx.doi.org/10.1080/10641963.2023.2202367 |
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