Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway

• Published in: Clinical and experimental hypertension (1993) Vol. 39; no. 1; pp. 34 - 41
• Main Authors: Gao, Hua, Cheng, Yuqing, Zong, Liguo, Huang, Linian, Qiao, Chenchen, Li, Wei, Gong, Beilei, Hu, Junfeng, Liu, Haitao, Wang, Xiaojing, Zhao, Chengling
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2017; Taylor & Francis Group
• Subjects: Animals; Aspirin; Aspirin - pharmacology; Aspirin - therapeutic use; Blood Pressure - drug effects; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; ERK1/2; Flavonoids - pharmacology; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - drug therapy; Hypertrophy, Right Ventricular - chemically induced; Hypertrophy, Right Ventricular - drug therapy; Male; MAP Kinase Signaling System - drug effects; Monocrotaline; Nitric Oxide Synthase Type III - drug effects; nonsteroidal anti-inflammatory drugs; Protein Kinase Inhibitors - pharmacology; pulmonary arterial hypertension; Pulmonary Artery - drug effects; Pulmonary Artery - pathology; Rats; Rats, Sprague-Dawley; Systole; Vascular Remodeling - drug effects; nonsteroidal anti-inflammatory drugs; Aspirin; ERK1/2; pulmonary arterial hypertension
• ISSN: 1064-1963; 1525-6006
• DOI: 10.1080/10641963.2016.1210620

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.