Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Urantide Prevents and Alleviates Monocrotaline Induced Pulmonary Arterial Hypertension in Wistar Rats.
Mei1, Yifang, Jin3, Hong, Wang2, Hao, Tian2, Wei, Zhao2, Yanping, Zhang2, Zhiyi
The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
The First Affiliated Hospital of Harbin Medical University, Harbin, China
The First Affiliated Hospital of Shantou University Medical College, Shantou, China
Pulmonary arterial hypertension (PAH) is a serious complication of connective tissue disease (CTD). Urotensin II (UII) has been confirmed to be the most powerful vasoconstrictor greater than endothelin-1, which may play an important role on PAH development.
To observe the effects of urantide, an UII receptor antagonist, on monocrotaline (MCT)-induced PAH in rats.
60 male Wistar rats were divided into six groups. For early treatment experiment, rats were divided into normal control group, MCT4w model group(MCT+saline×3wks from the 8th day of MCT-injection) and urantide early treatment group (MCT+urantide 10mg/kg/d×3wks from the 8th day of MCT-injection). For late treatment experiment, rats were dived as controls, MCT6w model group(MCT+saline×2wks 4 weeks after MCT injected once), and urantide late treatment group (MCT + urantide 10mg/kg/d×2wks 4 weeks after MCT injected once). The relaxation effects of urantide on the intralobar pulmonary artery rings of control and MCT 4wks model rats were investigated. Then, the mean pulmonary arterial pressures (mPAP) of rats in each group were measured by flow-directed pulmonary artery catheter. Pulmonary artery remodeling was detected by hematoxylin and eosin (HE) staining. The rats plasma endothelial nitric oxide synthase (eNOS) and nitric oxide(NO) levels in all six groups were assayed by ELISA kits.
Urantide dose-dependently relaxed the pulmonary artery rings of PAH model and normal rats. Moreover, L-NAME blocked the dilation response of urantide. Urantide reduced the mPAP in both early and late treatment groups and inhibited the pulmonary vascular remodeling remarkably. eNOS and NO levels in plasma elevated in both early and late treatment rats with urantide infusion.
Urantide effectively alleviated MCT induced PAH, at least partly, through mediating NO releasing, which provided a novel therapy for PAH.
To cite this abstract, please use the following information:
Mei, Yifang, Jin, Hong, Wang, Hao, Tian, Wei, Zhao, Yanping, Zhang, Zhiyi; Urantide Prevents and Alleviates Monocrotaline Induced Pulmonary Arterial Hypertension in Wistar Rats. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :618