PKR inhibitor imoxin prevents hypertension, endothelial dysfunction and cardiac and vascular remodelling in L-NAME-treated rats
Copyright © 2020 Elsevier Inc. All rights reserved..
AIMS: Hypertension is one of the leading causes of cardiovascular mortality and morbidity. It is associated with severe cardiac and vascular dysfunction. Double-stranded RNA-dependent protein kinase (PKR), is a known inducer of inflammation and apoptosis. However, no research has been done to elucidate the role of the PKR in an experimental model of hypertension, and related cardiovascular complications.
MAIN METHODS: L-NAME (NG-Nitro-L-arginine-methyl ester) was used to induce the hypertension. Imoxin treatment was given to Wistar rats for the four weeks along with the L-NAME, to investigate the influence on the hypertension. Changes in physiological parameter were assessed by recording non-invasive blood pressure. Expression of PKR and downstream markers for inflammation, fibrosis, and vascular damage in rat heart and aorta was determined by western blot and immunohistochemistry. Histological examination and fibrosis assessment were done by using assay kits. Vascular reactivity was determined by ex-vivo isometric tension studies on rat aortic rings.
KEY FINDINGS: L-NAME-treated rats showed a significant increase in PKR expression followed by cardiac damage and vascular alterations compared to that of control animals. Results of western blot and immunohistochemistry indicate a significant increase in the inflammatory markers downstream to PKR. Endothelium-dependent vascular relaxation was significantly impaired in L-NAME administered rats. All effects of the L-NAME were attenuated by selective inhibition of PKR by imoxin.
SIGNIFICANCE: Alterations in the heart and vasculature could be mediated in part by activation of the PKR pathway. Hence selective inhibition of PKR has therapeutic potential for combating hypertension and associated cardiovascular complications.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:262 |
|---|---|
| Enthalten in: |
Life sciences - 262(2020) vom: 01. Dez., Seite 118436 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kalra, Jaspreet [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.12.2020 Date Revised 14.12.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.lfs.2020.118436 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM315219351 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM315219351 | ||
| 003 | DE-627 | ||
| 005 | 20231225154433.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.lfs.2020.118436 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1050.xml |
| 035 | |a (DE-627)NLM315219351 | ||
| 035 | |a (NLM)32950570 | ||
| 035 | |a (PII)S0024-3205(20)31189-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kalra, Jaspreet |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PKR inhibitor imoxin prevents hypertension, endothelial dysfunction and cardiac and vascular remodelling in L-NAME-treated rats |
| 264 | 1 | |c 2020 | |
| 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 04.12.2020 | ||
| 500 | |a Date Revised 14.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a AIMS: Hypertension is one of the leading causes of cardiovascular mortality and morbidity. It is associated with severe cardiac and vascular dysfunction. Double-stranded RNA-dependent protein kinase (PKR), is a known inducer of inflammation and apoptosis. However, no research has been done to elucidate the role of the PKR in an experimental model of hypertension, and related cardiovascular complications | ||
| 520 | |a MAIN METHODS: L-NAME (NG-Nitro-L-arginine-methyl ester) was used to induce the hypertension. Imoxin treatment was given to Wistar rats for the four weeks along with the L-NAME, to investigate the influence on the hypertension. Changes in physiological parameter were assessed by recording non-invasive blood pressure. Expression of PKR and downstream markers for inflammation, fibrosis, and vascular damage in rat heart and aorta was determined by western blot and immunohistochemistry. Histological examination and fibrosis assessment were done by using assay kits. Vascular reactivity was determined by ex-vivo isometric tension studies on rat aortic rings | ||
| 520 | |a KEY FINDINGS: L-NAME-treated rats showed a significant increase in PKR expression followed by cardiac damage and vascular alterations compared to that of control animals. Results of western blot and immunohistochemistry indicate a significant increase in the inflammatory markers downstream to PKR. Endothelium-dependent vascular relaxation was significantly impaired in L-NAME administered rats. All effects of the L-NAME were attenuated by selective inhibition of PKR by imoxin | ||
| 520 | |a SIGNIFICANCE: Alterations in the heart and vasculature could be mediated in part by activation of the PKR pathway. Hence selective inhibition of PKR has therapeutic potential for combating hypertension and associated cardiovascular complications | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cardiovascular fibrosis | |
| 650 | 4 | |a Endothelial dysfunction | |
| 650 | 4 | |a Systolic blood pressure | |
| 650 | 4 | |a Vascular relaxation | |
| 650 | 7 | |a Antihypertensive Agents |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a imoxin |2 NLM | |
| 650 | 7 | |a eIF-2 Kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a NG-Nitroarginine Methyl Ester |2 NLM | |
| 650 | 7 | |a V55S2QJN2X |2 NLM | |
| 700 | 1 | |a Dasari, Deepika |e verfasserin |4 aut | |
| 700 | 1 | |a Bhat, Audesh |e verfasserin |4 aut | |
| 700 | 1 | |a Mangali, Sureshbabu |e verfasserin |4 aut | |
| 700 | 1 | |a Goyal, Srashti Gopal |e verfasserin |4 aut | |
| 700 | 1 | |a Jadhav, Kirtikumar B |e verfasserin |4 aut | |
| 700 | 1 | |a Dhar, Arti |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Life sciences |d 1965 |g 262(2020) vom: 01. Dez., Seite 118436 |w (DE-627)NLM000007579 |x 1879-0631 |7 nnns |
| 773 | 1 | 8 | |g volume:262 |g year:2020 |g day:01 |g month:12 |g pages:118436 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.lfs.2020.118436 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 262 |j 2020 |b 01 |c 12 |h 118436 | ||