Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway
This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a con...
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Format: | Article |
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Taylor & Francis Group
2017-01-01
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Series: | Clinical and Experimental Hypertension |
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Online Access: | http://dx.doi.org/10.1080/10641963.2016.1210620 |
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author | Hua Gao Yuqing Cheng Liguo Zong Linian Huang Chenchen Qiao Wei Li Beilei Gong Junfeng Hu Haitao Liu Xiaojing Wang Chengling Zhao |
author_facet | Hua Gao Yuqing Cheng Liguo Zong Linian Huang Chenchen Qiao Wei Li Beilei Gong Junfeng Hu Haitao Liu Xiaojing Wang Chengling Zhao |
author_sort | Hua Gao |
collection | DOAJ |
description | This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway. |
first_indexed | 2024-03-11T23:46:29Z |
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issn | 1064-1963 1525-6006 |
language | English |
last_indexed | 2024-03-11T23:46:29Z |
publishDate | 2017-01-01 |
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series | Clinical and Experimental Hypertension |
spelling | doaj.art-e3d737f155564f4bba6f798adaa548ec2023-09-19T09:24:44ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062017-01-01391344110.1080/10641963.2016.12106201210620Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathwayHua Gao0Yuqing Cheng1Liguo Zong2Linian Huang3Chenchen Qiao4Wei Li5Beilei Gong6Junfeng Hu7Haitao Liu8Xiaojing Wang9Chengling Zhao10First Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseZaozhuang Municipal HospitalFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Municipal Hospital of BengbuFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseFirst Affiliated Hospital of Bengbu Medical College, Anhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseThis study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.http://dx.doi.org/10.1080/10641963.2016.1210620aspirinerk1/2nonsteroidal anti-inflammatory drugspulmonary arterial hypertension |
spellingShingle | Hua Gao Yuqing Cheng Liguo Zong Linian Huang Chenchen Qiao Wei Li Beilei Gong Junfeng Hu Haitao Liu Xiaojing Wang Chengling Zhao Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway Clinical and Experimental Hypertension aspirin erk1/2 nonsteroidal anti-inflammatory drugs pulmonary arterial hypertension |
title | Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway |
title_full | Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway |
title_fullStr | Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway |
title_full_unstemmed | Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway |
title_short | Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway |
title_sort | aspirin attenuates monocrotaline induced pulmonary arterial hypertension in rats by suppressing the erk mapk pathway |
topic | aspirin erk1/2 nonsteroidal anti-inflammatory drugs pulmonary arterial hypertension |
url | http://dx.doi.org/10.1080/10641963.2016.1210620 |
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