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pubmed-article:21396478pubmed:abstractTextPulmonary arterial hypertension (PAH) is a serious disorder with poor prognosis. Urotensin II (UII) has been confirmed to be powerful vasoconstrictor than endothelin-1, which may play an important role in PAH development. The aim of this study is to observe the effects of urantide, a 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, MCT(4w) model group (MCT + saline × 3 wks from the 8th day of MCT injection) and urantide early treatment group (MCT + urantide 10 ?g/kg/d × 3 wks, 1 week after MCT injection once). For late treatment experiment, rats were divided as controls, MCT(6w) model group (MCT + saline × 2 wks, 4 weeks after MCT injection once) and urantide late treatment group (MCT + urantide 10 ?g/kg/d × 2 wks, 4 weeks after MCT injection once). At the end of experiments, mean pulmonary arterial pressures (mPAP) and mean blood pressure (MBP) of rats in each group were measured by catheterization. Right ventricular weight ratio was also weighed. Relaxation effects of urantide on intralobar pulmonary arterial rings of normal control and MCT(4w) model rats were investigated. Pulmonary artery remodeling was detected by hematoxylin and eosin (HE) staining and immunohistochemistry analysis. Serum nitric oxide (NO) levels in all six groups were assayed by ELISA kits. Urantide markedly reduced the mPAP levels of MCT induced PAH in both early and late treatment groups. It didn't change the MBP. Urantide dose-dependently relaxed the pulmonary arterial rings of normal control and MCT(4w) model rats. Moreover, N(G)-Nitro-l-arginine Methyl Ester (l-NAME) blocked the dilation response induced by urantide. In addition, urantide inhibited the pulmonary vascular remodeling remarkably. Serum NO level elevated in both early and late treatment rats with urantide infusion. These results suggest that urantide effectively alleviated MCT induced rats PAH may through relaxing pulmonary arteries and inhibiting pulmonary vascular remodeling. NO pathway might be one of the mechanisms in urantide induced pulmonary artery dilation. Thus, it is expected that urantide may be a novel therapy for PAH.lld:pubmed
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pubmed-article:21396478pubmed:authorpubmed-author:WangHanHlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:WangHaoHlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:JinHongHlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:TianWeiWlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:ZhangZhiyiZlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:ZhaoYanpingYlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:MeiYifangYlld:pubmed
pubmed-article:21396478pubmed:authorpubmed-author:MengFanchaoFlld:pubmed
pubmed-article:21396478pubmed:copyrightInfoCopyright © 2011 Elsevier Ltd. All rights reserved.lld:pubmed
pubmed-article:21396478pubmed:issnTypeElectroniclld:pubmed
pubmed-article:21396478pubmed:volume24lld:pubmed
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pubmed-article:21396478pubmed:pagination386-93lld:pubmed
pubmed-article:21396478pubmed:dateRevised2011-11-17lld:pubmed
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pubmed-article:21396478pubmed:year2011lld:pubmed
pubmed-article:21396478pubmed:articleTitleUrantide alleviates monocrotaline induced pulmonary arterial hypertension in Wistar rats.lld:pubmed
pubmed-article:21396478pubmed:affiliationThe First Affiliated Hospital of Harbin Medical University, 23 You Zheng St., Nan Gang District, Harbin 150001, China. myfyxd@163.comlld:pubmed
pubmed-article:21396478pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21396478pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed