| Arachidonic acid inhibits Na(+)-K(+)-ATPase via cytochrome P-450, lipooxygenase and protein kinase C-dependent pathways in sheep pulmonary artery. | |
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MedLine Citation:
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PMID: 22155164 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The purpose of the study was to examine whether arachidonic acid inhibits vascular Na(+)-K(+)-ATPase in pulmonary vasculature and if so, what are the mechanisms involved. Functional Na(+)-K(+)-ATPase activity was studied in terms of K(+)-induced relaxation in sheep pulmonary arterial rings contracted with K(+)-free solution and 5-HT. Arachidonic acid (10-100μM) caused concentration-dependent inhibition of KCl-induced relaxations and also increased basal arterial tone. Cytochrome P-450 inhibitor, 17-Octadecynoic acid (17-ODYA) completely reversed the arachidonic acid (30μM)-induced inhibition of KCl relaxation. Further, in the presence of HET0016, a selective blocker of 20-Hydroxyeicosatetraenoic acid (20-HETE), arachidonic acid-induced inhibition of KCl relaxation was not evident. Accordingly, 20-HETE, a cytochrome P-450 metabolite of arachidonic acid, also significantly attenuated KCl-induced relaxations. Norhydihydroguaiaretic acid (NDGA), a lipooxygenase inhibitor however partially restored the relaxation to K(+), impaired in the presence of arachidonic acid (30μM).On the other hand, cyclooxygenase inhibitor indomethacin failed to reverse the inhibitory effect of arachidonic acid on KCl-induced relaxation. Staurosporine, a protein kinase C inhibitor, completely reversed the inhibitory effect of arachidonic acid and 20-HETE on K(+)-induced relaxation. In conclusion, the results suggest that 20-HETE, a cytochrome P-450 metabolite of arachidonic acid has a predominant role in the inhibition of functional Na(+)-K(+)-ATPase activity in the sheep pulmonary artery, while the lipooxygenase pathway has a secondary role. It is also evident that protein kinase C is involved in the inhibition of Na(+)-K(+)-ATPase by arachidonic acid/20-HETE in sheep pulmonary artery. |
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Authors:
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Thakur Uttam Singh; Soumen Choudhury; Subhashree Parida; Bhojane Somnath Maruti; Santosh Kumar Mishra |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-3 |
Journal Detail:
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Title: Vascular pharmacology Volume: - ISSN: 1879-3649 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101130615 Medline TA: Vascul Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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