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Videomorphometric Analysis of Hypoxic Pulmonary Vasoconstriction of Intra-pulmonary Arteries Using Murine Precision Cut Lung Slices
Published on: January 14, 2014
Role of dynorphin in hypoxic pulmonary hypertension
Juan Li1, Xiaojie Liang1, Yaguang Zhou1
1Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Abstract:
Previously study showed κ-opioid receptor stimulation with exogenous κ-opioid receptor agonist elicited a protective effect against hypoxic pulmonary hypertension (HPH). However, the effect of endogenous κ-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 κ-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 κ-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 AngII 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. κ-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 κ-opioid receptor.
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