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 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
|---|---|
| Enthalten in: |
Clinical and experimental hypertension (New York, N.Y. : 1993) - 45(2023), 1 vom: 31. Dez., Seite 2202367 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhu, Jun [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
4-phenylbutylamine |
|---|
| Anmerkungen: |
Date Completed 08.05.2023 Date Revised 08.05.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1080/10641963.2023.2202367 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356475670 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356475670 | ||
| 003 | DE-627 | ||
| 005 | 20231226070536.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/10641963.2023.2202367 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1188.xml |
| 035 | |a (DE-627)NLM356475670 | ||
| 035 | |a (NLM)37144334 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhu, Jun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibition of endoplasmic reticulum stress restores the balance of renal RAS components and lowers blood pressure in the spontaneously hypertensive rats |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.05.2023 | ||
| 500 | |a Date Revised 08.05.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Endoplasmic reticulum stress | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Renin-angiotensin system | |
| 650 | 4 | |a hypertension | |
| 650 | 4 | |a kidney | |
| 650 | 7 | |a 4-phenylbutylamine |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Shao, Anjing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chunyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Chensi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hongyong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical and experimental hypertension (New York, N.Y. : 1993) |d 1993 |g 45(2023), 1 vom: 31. Dez., Seite 2202367 |w (DE-627)NLM075081989 |x 1525-6006 |7 nnns |
| 773 | 1 | 8 | |g volume:45 |g year:2023 |g number:1 |g day:31 |g month:12 |g pages:2202367 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/10641963.2023.2202367 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 45 |j 2023 |e 1 |b 31 |c 12 |h 2202367 | ||