Role of dynorphin in hypoxic pulmonary hypertension

被引：6

作者：

Li, Juan ^{[1
]}

Liang, Xiaojie ^{[1
]}

Zhou, Yaguang ^{[1
]}

Zhang, Shumiao ^{[1
]}

Yang, Fan ^{[1
]}

Guo, Haitao ^{[1
]}

Fan, Rong ^{[1
]}

Feng, Na ^{[1
]}

Jia, Min ^{[1
]}

Wang, Yueming ^{[1
]}

Liu, Mingchao ^{[2
]}

Pei, Jianming ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Natl Key Discipline Cell Biol, Dept Physiol, Xian 710032, Shaanxi Provinc, Peoples R China

[2] Fourth Mil Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Xian 710032, Shaanxi Provinc, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2016年 / 791卷

基金：

中国国家自然科学基金;

关键词：

Dynorphin A; Opioid receptor; Pulmonary artery hypertension; Hypoxia; OPIOID RECEPTOR; U50,488H; RATS; ARTERY; EXPRESSION; HEART;

D O I：

10.1016/j.ejphar.2016.08.019

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Previously study showed kappa-opioid receptor stimulation with exogenous kappa-opioid receptor agonist elicited a protective effect against hypoxic pulmonary hypertension (HPH). However, the effect of endogenous kappa-opioid receptor agonist dynorphin A on HPH remains unclear. This study was to determine the role of dynorphin in HPH. Hypoxia for 2 weeks induced HPH. Compared with the HPH group, the HPH + nor-BNI (a selective kappa-opioid receptor antagonist) group showed a significant increase in mean pulmonary arterial pressure (mPAP). Exogenous treatment with dynorphin A 1-13 significantly decreased mPAP in HPH rat. In addition, we evaluated the effect of exogenous kappa-opioid receptor agonist U50,488H on mPAP. The anti-HPH effect of dynorphin A was less than that of U50,488H. Meanwhile, level of dynorphin A in serum and lung was increased during hypoxia for 2 weeks, while it decreased after hypoxia for 4 weeks. In addition, both the level of ET-1 and Angll were increased during hypoxia. Dynorphin A 1-13 and U50,488H time-dependently relaxed pulmonary artery from both normal and HPH rats. The relaxation of dynorphin A was less than that of U50,488H. Dynorphin A 1-13 inhibited the proliferation of pulmonary artery smooth muscle cells (PASMCs) during hypoxia, which was blocked by nor-BNI. kappa-opioid receptor expression increased in PASMCs in both normoxia exposed to dynorphin A 1-13 and during hypoxia. Hypoxia-induced increase was enhanced by dynorphin A 1-13 and abolished by nor-BNI. In conclusion, endogenous dynorphin A released in the early stage of hypoxia plays a protective effect against HPH via stimulation of kappa-opioid receptor. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：78 / 84

页数：7

共 34 条

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