Document Detail


Sertraline protects against monocrotaline-induced pulmonary hypertension in rats.
MedLine Citation:
PMID:  17042913     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Serotonin (5-HT), as a type of mitogen for smooth muscle cells, plays an important role in the development of pulmonary hypertension. It is known that selective serotonin re-uptake inhibitors (SSRI) inhibit 5-HT internalization. Therefore, the aim of the present study was to investigate the protective effect and mechanism of the SSRI sertraline against pulmonary hypertension. 2. Monocrotaline (MCT)-induced chronic 'inflammatory' pulmonary hypertension in Wistar rats was established. Pulmonary haemodynamic measurement and lung tissue morphological investigations were undertaken. Serotonin transporter (SERT) mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR). 3. The results showed that pulmonary artery pressure (PAP) was significantly increased by MCT treatment from 12.6 +/- 2.1 to 20.1 +/- 3.4 mmHg (P < 0.01 vs control) and sertraline attenuated the MCT-induced increase in PAP from 20.1 +/- 3.4 to 16.4 +/- 1.8 mmHg (P < 0.05 vs MCT). The right ventricular index was increased in the MCT-treated group from 0.32 +/- 0.04 to 0.51 +/- 0.09 (P < 0.01 vs control) and was reduced to 0.42 +/- 0.04 by sertraline (P < 0.05 vs MCT). The degree of muscularization of the pulmonary artery in the MCT-treated group was significantly higher than control (P < 0.01) and was decreased by sertraline (P < 0.01 vs MCT). The RT-PCR assay showed that MCT increased SERT mRNA expression from 0.86 +/- 0.08 to 0.99 +/- 0.06 (P < 0.05 vs control), which was attenuated by sertraline (0.82 +/- 0.09; P < 0.05 vs MCT). 4. In conclusion, the SSRI sertraline protects against MCT-induced pulmonary hypertension by decreasing PAP, right ventricular index and pulmonary artery remodelling, which may be related to a reduction in SERT mRNA.
Authors:
Xue-Qin Li; Yang Hong; Yun Wang; Xin-Hua Zhang; Huai-Liang Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  33     ISSN:  0305-1870     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-17     Completed Date:  2007-02-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  1047-51     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, China Medical University, Shenyang, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Expression Regulation
Hypertension, Pulmonary / chemically induced*,  prevention & control*
Male
Monocrotaline / toxicity*
RNA, Messenger
Rats
Rats, Wistar
Serotonin Plasma Membrane Transport Proteins / metabolism
Serotonin Uptake Inhibitors / therapeutic use*
Sertraline / therapeutic use*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Serotonin Plasma Membrane Transport Proteins; 0/Serotonin Uptake Inhibitors; 0/Slc6a4 protein, rat; 315-22-0/Monocrotaline; 79617-96-2/Sertraline

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