title: Assessment of the endothelial functions in monocrotaline-induced pulmonary hypertension.
abstract: Pulmonary hypertension (PH) is a life-threatening disease that causes endothelial dysfunction in the pulmonary vascular bed. Systemic endothelial dysfunction has also been reported in PH. This study compared the systemic and pulmonary vascular responses and some blood biomarkers of endothelial function in monocrotaline (MCT)-induced PH of rats. It also investigated the effect of sildenafil and iloprost treatment. MCT application induced elevation in the right ventricular pressures of the rat heart that had been reversed by sildenafil and iloprost treatment. Acetylcholine-induced endothelium-dependent relaxations of the isolated pulmonary artery were decreased in the PH group and this failure was reversed by sildenafil and iloprost treatment. Acetylcholine-induced endothelium-dependent relaxations of the isolated thoracic aorta were similar in all groups. Serotonin-induced contractions of the pulmonary artery were augmented by PH. In the isolated aorta, serotonin-stimulated contraction was not different in the control and MCT groups, but sildenafil and iloprost treatment decreased serotonin responses. The nitric oxide (NO) level in systemic circulation was not significantly changed by PH. However, sildenafil and iloprost treatments caused a decrease in the plasma level of NO. Asymmetric dimethylarginine levels in plasma were significantly decreased after MCT application and were not recovered by sildenafil and iloprost treatment. Total antioxidant capacity and H2S level of plasma were similar in all groups. Results of this study showed that MCT-induced PH caused specific toxic effects on pulmonary vasculature without any functional effects on the aorta. In addition, it was also demonstrated that sildenafil and iloprost treatments were effective in the MCT-induced PH.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey.
authors.forename: Basar
authors.initials: B
authors.lastname: Sirmagul
authors.forename: Sinem
authors.initials: S
authors.lastname: Ilgin
authors.forename: Ozlem
authors.initials: O
authors.lastname: Atli
authors.forename: Suzan Emel
authors.initials: SE
authors.lastname: Usanmaz
authors.forename: Emine
authors.initials: E
authors.lastname: Demirel-Yilmaz
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006862:Hydrogen Sulfide / Q000097:blood; D006976:Hypertension, Pulmonary / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D016686:Monocrotaline; D009569:Nitric Oxide / Q000097:blood; D010879:Piperazines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D016686:Monocrotaline; D001120:Arginine; D000068677:Sildenafil Citrate; D016285:Iloprost; D006862:Hydrogen Sulfide