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Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor
Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whet...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019878/ https://www.ncbi.nlm.nih.gov/pubmed/29962859 http://dx.doi.org/10.4196/kjpp.2018.22.4.447 |
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author | Cha, Seung Ah Park, Byung Mun Kim, Suhn Hee |
author_facet | Cha, Seung Ah Park, Byung Mun Kim, Suhn Hee |
author_sort | Cha, Seung Ah |
collection | PubMed |
description | Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576 µg/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor (AT(2)R) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as TNF-α, MCP-1, IL-1β, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via AT(2)R. |
format | Online Article Text |
id | pubmed-6019878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-60198782018-07-01 Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor Cha, Seung Ah Park, Byung Mun Kim, Suhn Hee Korean J Physiol Pharmacol Original Article Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576 µg/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor (AT(2)R) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as TNF-α, MCP-1, IL-1β, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via AT(2)R. The Korean Physiological Society and The Korean Society of Pharmacology 2018-07 2018-06-25 /pmc/articles/PMC6019878/ /pubmed/29962859 http://dx.doi.org/10.4196/kjpp.2018.22.4.447 Text en Copyright © Korean J Physiol Pharmacol http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Cha, Seung Ah Park, Byung Mun Kim, Suhn Hee Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor |
title | Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor |
title_full | Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor |
title_fullStr | Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor |
title_full_unstemmed | Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor |
title_short | Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor |
title_sort | angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type ii receptor |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019878/ https://www.ncbi.nlm.nih.gov/pubmed/29962859 http://dx.doi.org/10.4196/kjpp.2018.22.4.447 |
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