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    Pyrrolidine dithiocarbamate attenuates the development of monocrotaline-induced pulmonary arterial hypertension
    (Elsevier Gmbh, Urban & Fischer Verlag, 2013) Yavuz, Taner; Uzun, Ozge; Macit, Asli; Comunoglu, Cem; Yavuz, Ozlem; Silan, Coskun; Yuksel, Hatice
    We aimed to demonstrate the potential protective effects of pyrrolidine dithiocarbamate (PDTC) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Adult male rats were randomly assigned to 4 groups: control group, MCT-treated rats only, MCT-injected rats treated with PDTC, and PDTC-treated rats only. Blood and tissue samples were collected after the sacrifice. Levels of malondialdehyde (MDA) were measured by using the thiobarbituric acid method. Total antioxidant status (TAS) was determined using a commercially available ImAnOx kit. A histopathological evaluation was accomplished by scoring the degree of severity. Endothelial damage of the main pulmonary artery was evaluated by immunohistochemical labeling of endothelial cells using anti-rat endothelial cell antigen 1 (RECA-1) antibody. MCT-induced right ventricular hypertrophy (RVH) was reduced significantly in the MCT + PDTC-treated group. MDA levels were significantly lowered in the MCT + PDTC-treated group. TAS was significantly higher in the MCT + PDTC-treated group when compared with the rats with PAH. Histopathological examination demonstrated that PDTC treatment reduced the development of inflammation, hemorrhage and congestion, and collagen deposition. In conclusion, PDTC attenuated PAH and protected pulmonary endothelium in rats administered MCT. These findings suggest that PDTC treatment may provide a new effective therapeutic approach in the treatment of PAH. (C) 2013 Elsevier GmbH. All rights reserved.
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    The Role of Gi and Gs Proteins in Hypoxic Vasoconstriction of Lamb Isolated Pulmonary Artery Rings
    (Kafkas Univ, Veteriner Fakultesi Dergisi, 2014) Erbas, Mete; Balbay, Oner; Uzun, Ozge; Gulec Balbay, Ege; Silan, Coskun
    Hypoxic pulmonary vasoconstriction (HPV) is an intrapulmonary adaptive mechanism that matches alveolar ventilation to perfusion. However during prolonged alveolar hypoxia HPV occurs with many pulmonary diseases. Despite intensive studies, cellular mechanisms of HPV are still not well defined. G proteins are a family of membrane-associated proteins believed to be involved in the transduction of various signals including the regulation of vascular tonus. In this study, we aimed to determine the contribution of G(i) and G(s) proteins in hypoxic vasoconstriction of lamb isolated pulmonary artery rings. Pulmonary arteries were isolated from left lower lobe of freshly slaughtered lamb. Arteries suspended in an organ bath filled with Krebs-Henseleit solution and isometric contraction recorded continuously via an isometric transducer connected to a computerised polygraphy system. The solution aerated with 75% N-2 - 20% O-2 - 5% CO2 (normoxic) and 95% N-2 - 5% CO2 (hypoxic) pO(2) of bathing medium was measured continuosly using an oxygen electrode. Pertussis toxin and cholera toxin were used to investigate the role of G(i) and G(s) proteins. In the present study, we observed that hypoxia had no effect on resting force in large artery rings, but it caused a further contraction (1.7 +/- 0.5 mN/mm(2), n=10) in 3 mu M 5-HT precontracted pulmonary arteries rings. Hypoxic vasoconstriction was inhibited by preincubation with 2 mu g/ml cholera toxins (from 2.6 +/- 0.4 mN/mm(2), to 1.0 +/- 0.4 mN/mm(2), n=6) and potentiated by preincubation with pertussis toxins (2 mu g/ml) (from 0.6 +/- 0.4 mN/mm(2), to 1.7 +/- 0.3 mN/mm(2), n=6). These results indicate that signal transduction mediated by G(i) and G(s) proteins may be an important mechanism in the hypoxic vasoconstriction in lamb isolated large pulmonary arteries.