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Role of dynorphin in hypoxic pulmonary hypertension.
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- Additional Information
- Source:
Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE
- Publication Information:
Publication: 2005- : Amsterdam : Elsevier Science
Original Publication: Amsterdam, North Holland Pub. Co.
- Subject Terms:
Dynorphins/
*metabolism ;
Hypertension, Pulmonary/
*metabolism ;
Hypertension, Pulmonary/
*pathology;
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/
pharmacology ;
Angiotensin II/
blood ;
Animals ;
Blood Pressure/
drug effects ;
Cell Hypoxia/
drug effects ;
Cell Proliferation/
drug effects ;
Dynorphins/
blood ;
Dynorphins/
pharmacology ;
Endothelin-1/
blood ;
Gene Expression Regulation/
drug effects ;
Humans ;
Hypertension, Pulmonary/
blood ;
Hypertension, Pulmonary/
physiopathology ;
Lung/
drug effects ;
Lung/
metabolism ;
Male ;
Myocytes, Smooth Muscle/
drug effects ;
Myocytes, Smooth Muscle/
pathology ;
Pulmonary Artery/
drug effects ;
Pulmonary Artery/
physiopathology ;
Rats ;
Rats, Sprague-Dawley ;
Receptors, Opioid, kappa/
metabolism - 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.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
- Contributed Indexing:
Keywords: Dynorphin A; Hypoxia; Opioid receptor; Pulmonary artery hypertension
- Accession Number:
0 (Endothelin-1)
0 (Receptors, Opioid, kappa)
11128-99-7 (Angiotensin II)
67198-13-4 (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer)
74913-18-1 (Dynorphins)
- Publication Date:
Date Created: 20160829 Date Completed: 20170328 Latest Revision: 20220317
- Publication Date:
20221213
- Accession Number:
10.1016/j.ejphar.2016.08.019
- Accession Number:
27568355
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