5743

PTGS2

COX-2|COX2|GRIPGHS|PGG/HS|PGHS-2|PHS-2|hCox-2;prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase);PTGS2;prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)

PGH synthase 2|PHS II|cyclooxygenase 2b|prostaglandin G/H synthase 2|prostaglandin H2 synthase 2

1q25.2-q25.3

protein-coding

Count: Ptgs2; 29527

AIM: To study the effect of chronic hypoxic hypercapnia on expression of COX-2 mRNA in pulmonary arterioles. METHODS: SD rats were randomly divided into two groups: control group and hypoxic hypercapnic group. COX-2 mRNA was observed in pulmonary arterioles by the technique of in situ hybridization. RESULTS: mPAP, weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) and COX-2 mRNA in pulmonary arterioles were much higher in rats of hypoxic hypercapnic group than those of control group. Light microscopy showed that vessel smooth muscle cell hypertrophy and vessel cavity straightness were found in hypoxic hypercapnic group. CONCLUSION: Changes of expressions of COX-2 mRNA may regulate hypoxic hypercapnic pulmonary hypertension.

PURPOSE: Chronic pulmonary hypertension (PH) therapy is poorly investigated in intensive care. Our aim was to evaluate haemodynamic and neuroendocrine effects of the dual endothelin-1 (ET-1) blocker tezosentan in monocrotaline (MCT)-induced PH. METHODS: Male Wistar rats (180-200 g, n = 194) randomly received 60 mg kg(-1) MCT or vehicle, subcutaneously, and 2 days later, a subgroup of MCT-injected rats was gavaged with 300 mg kg(-1) day(-1) bosentan (MCT BOS, n = 46), while another (MCT, n = 125) and control rats (Ctrl, n = 23) received vehicle. At 25-30 days, 48 h after interrupting bosentan, rats randomly underwent either a dose-response evaluation (0.5-20 mg kg(-1), n = 7 each group) or a 4 h perfusion of tezosentan (20 mg kg(-1) in 10 min + 10 mg g(-1) h(-1)) or vehicle (n = 8 per group, each). Haemodynamics, including blood gas analysis, were evaluated after thoracotomy under anaesthesia. After plasma, right ventricle (RV) and lung collection, plasma ET-1, cytokines, nitrate and 6-keto-PGF1alpha, and lung and right ventricular gene expression and cyclooxygenase (COX) and nitric oxide synthase (NOS) activities were quantified. RESULTS: Monocrotaline resulted in PH, RV dilation and decreased cardiac output (CO) that were attenuated in MCT BOS. pulmonary hypertension was attenuated by tezosentan without systemic hypotension. Tezosentan increased CO without changing ventilation-perfusion matching. Both bosentan and tezosentan reduced ET-1 and cytokine plasma levels and tissue expression, and inducible NOS and COX-2 RV activities. Bosentan increased nitrate plasma levels and non inducible NOS activities whereas tezosentan decreased circulating 6-keto-PGF1alpha but increased lung COX-1 activity. CONCLUSIONS: Tezosentan may be useful for haemodynamic handling and bosentan replacement in critically ill PH patients exerting important beneficial neuroendocrine and anti-inflammatory actions.