SERTRALINE PROTECTS AGAINST MONOCROTALINE-INDUCED PULMONARY HYPERTENSION IN RATS
Professor Huai-Liang Wang, Department of Clinical Pharmacology, China Medical University, 92# The 2nd North Road, Heping District, Shenyang 110001, China. Email: email@example.com
- 1Serotonin (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.
- 2Monocrotaline (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).
- 3The 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).
- 4In 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.