Sertraline protects against monocrotaline-induced pulmonary hypertension in rats.
ABSTRACT 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.
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ABSTRACT: Serotonin promotes pulmonary arterial vasoconstriction and pulmonary arterial smooth muscle cell proliferation, thereby having the potential to increase pulmonary arterial blood pressure. Although serotonin reuptake inhibitors (SRIs) might inhibit further deterioration in patients with manifest pulmonary arterial hypertension, they may induce pulmonary hypertension in healthy newborns after fetal exposure. As it is unclear whether treatment with SRIs affects pulmonary hemodynamics in adults without pulmonary hypertension, the aim of the present study was to investigate the effect of SRIs on pulmonary hemodynamics in such subjects. Sixteen patients with stable angina pectoris scheduled for first time coronary artery bypass grafting were included in the study. Of these 8 were currently treated with an SRI (the SRI group) and 8 were not (the control group). Pulmonary arterial pressures were measured before induction of anesthesia by means of a pulmonary artery catheter. Serotonin transporter and 5-HT(2A) receptor gene polymorphisms and platelet 5-HT(2A) receptor expression were studied to elucidate their possible role as modifying factors. No patients in any of the groups had pulmonary arterial hypertension. Mean pulmonary artery pressure was 15.0 mmHg in the SRI group and 14.5 mmHg in the control group (P = 0.50; 95% confidence interval for the difference, -2.9 to +3.9 mmHg). Neither were there any significant differences between the groups for any of the other hemodynamic variables studied. The various gene polymorphisms and the extent of platelet 5-HT(2A) receptor expression did not influence the hemodynamic variables. SRI treatment did not significantly influence pulmonary hemodynamics in patients without pulmonary hypertension. Serotonin; Selective serotonin reuptake inhibitors; Pulmonary hemodynamics; Pulmonary hypertension.Journal of Clinical Medicine Research 10/2011; 3(5):230-8. DOI:10.4021/jocmr654w
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ABSTRACT: Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients.BioMed Research International 03/2010; 2010:702836. DOI:10.1155/2010/702836 · 2.71 Impact Factor
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ABSTRACT: Two recent studies linking in utero exposure to selective serotonin reuptake inhibitors (SSRIs) with persistent pulmonary hypertension of the newborn (PPHN), a potentially serious but rare respiratory illness, have made clinicians and patients more reluctant to use SSRIs during pregnancy. However, additional clinical studies have associated maternal depression rather than SSRI exposure as a risk factor for PPHN. This review summarizes the current knowledge regarding PPHN pathophysiology, including the role of serotonin and genetic risk factors; the effects of SSRIs on pulmonary vasculature; the possible link between SSRIs and PPHN; and the diagnosis, clinical management, and prognosis of PPHN.American Journal of Psychiatry 02/2012; 169(2):134-40. DOI:10.1176/appi.ajp.2011.11040553 · 13.56 Impact Factor