title: Urotensin inhibition with palosuran could be a promising alternative in pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50-125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.
authors.affiliation: Department of Rheumatology, School of Medicine, Sahinbey Medical Center, Gaziantep University, Gaziantep, 27310, Turkey.
authors.forename: Ahmet Mesut
authors.initials: AM
authors.lastname: Onat
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Pehlivan
authors.forename: Ibrahim Halil
authors.initials: IH
authors.lastname: Turkbeyler
authors.forename: Tuncer
authors.initials: T
authors.lastname: Demir
authors.forename: Davut Sinan
authors.initials: DS
authors.lastname: Kaplan
authors.forename: Ali Osman
authors.initials: AO
authors.lastname: Ceribasi
authors.forename: Mustafa
authors.initials: M
authors.lastname: Orkmez
authors.forename: Ediz
authors.initials: E
authors.lastname: Tutar
authors.forename: Seyithan
authors.initials: S
authors.lastname: Taysi
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sayarlioglu
authors.forename: Bunyamin
authors.initials: B
authors.lastname: Kisacik
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D001160:Arterioles / Q000187:drug effects; D019332:Endothelin-1 / Q000097:blood; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014579:Urotensins / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D019332:Endothelin-1; D011804:Quinolines; D053773:Transforming Growth Factor beta1; D014579:Urotensins; D016686:Monocrotaline; D014508:Urea; C029677:urotensin II; C493249:1-(2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl)-3-(2-methylquinolin-4-yl)urea