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Aspirin Attenuates Pulmonary Arterial Hypertension in Rats by Reducing Plasma 5-Hydroxytryptamine Levels

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Abstract

Pulmonary arterial hypertension (PAH) is characterized by increasing pulmonary pressure, right ventricular failure, and death. The typical pathological changes include medial hypertrophy, intimal fibrosis and in situ thrombosis. Serotonin (5-HT) and other factors contribute to the development of pathologic lesions. Aspirin (ASA), a platelet aggregation inhibitor, inhibits 5-HT release from platelets. The aim of this study was to determine the efficacy of ASA in preventing or attenuating PAH. Sprague–Dawley rats injected with monocrotaline (MCT) developed severe PAH within 31 days. One hundred forty rats were randomized to receive either vehicle or ASA (0.5, 1, 2, or 4 mg/kg/day). The pre-ASA group was treated with ASA (1 mg/kg/day) for 30 days before the MCT injection. Thirty-one days after the injection (day 61 for the pre-ASA group), pulmonary arterial pressure (PAP), right ventricular hypertrophy and pulmonary arteriole thickness were measured. Plasma 5-HT was measured by high-performance liquid chromatography. Aspirin suppressed PAH and increased the survival rate compared with the control group (84 vs. 60%, P < 0.05). Aspirin treatment also reduced right ventricular hypertrophy and pulmonary arteriole proliferation in ASA-treated PAH model. In addition, plasma 5-HT was decreased in our ASA-treated PAH model. The degree of 5-HT reduction was associated with systolic PAP, right ventricular hypertrophy and wall thickness of pulmonary arterioles in rats. These results showed that ASA treatment effectively attenuated MCT-induced pulmonary hypertension, right ventricular hypertrophy, and occlusion of the pulmonary arteries. The effects of ASA was associated with a reduction of 5-HT.

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Abbreviations

ASA:

Aspirin

IPAH:

Idiopathic pulmonary arterial hypertension

HPLC:

High-performance liquid chromatography

LV:

Left ventricle

MCT:

Monocrotaline

mPAP:

Mean pulmonary arterial pressure

mSAP:

Mean systemic arterial pressure

PAH:

Pulmonary arterial hypertension

PASMC:

Pulmonary arterial smooth muscle cell

PDE-5:

Phosphodiesterase-5

RV:

Right ventricle

RVHI:

Right ventricular hypertrophy index

RVSP:

Right ventricular systolic pressure

S:

Septum

SERT:

Serotonin reuptake transporter

sPAP:

Systolic pulmonary arterial pressure

WA %:

Percent wall area

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Acknowledgments

We thank Dr. Cai Yong for his help with statistics, Dr. Lin Peisen for help with the rat experiments and Mr. David Proctor for English revising. This study was supported by a grant from the Shanghai Municipal Health Bureau (2007103).

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Authors and Affiliations

  1. Cardiovascular Department, Renji Hospital, Shanghai Jiaotong University School of Medicine, Dong Fang Road 1630, Shanghai, 200127, China

    Lan Shen, Jieyan Shen, Jun Pu & Ben He

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  1. Lan Shen
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  2. Jieyan Shen
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Correspondence to Ben He.

Additional information

Jieyan Shen is the principle investigator of the original study; she is the co-first authors of this article.

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Shen, L., Shen, J., Pu, J. et al. Aspirin Attenuates Pulmonary Arterial Hypertension in Rats by Reducing Plasma 5-Hydroxytryptamine Levels. Cell Biochem Biophys 61, 23–31 (2011). https://doi.org/10.1007/s12013-011-9156-x

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