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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Main Authors: Hua Gao, Yuqing Cheng, Liguo Zong, Linian Huang, Chenchen Qiao, Wei Li, Beilei Gong, Junfeng Hu, Haitao Liu, Xiaojing Wang, Chengling Zhao
Format: Article
Language:English
Published: Taylor & Francis Group 2017-01-01
Series:Clinical and Experimental Hypertension
Subjects:
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.
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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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