Arachidonic acid inhibits Na⁺-K⁺-ATPase via cytochrome P-450, lipoxygenase and protein kinase C-dependent pathways in sheep pulmonary artery

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• 作者：Thakur Uttam Singh ; ^{tusingh80@gmail.com} ; Soumen Choudhury ; Subhashree Parida ; Bhojane Somnath Maruti ; Santosh Kumar Mishra
• 关键词：Arachidonic acid ; Na+&ndash ; K+&ndash ; ATPase ; Sheep ; Pulmonary artery
• 刊名：Vascular Pharmacology
• 出版年：2012
• 出版时间：January-February 2012
• 年：2012
• 卷：56
• 期：1-2
• 页码：84-90
• 全文大小：662 K

文摘

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 (10-100 ¦ÌM) 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 (30 ¦ÌM)-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 lipoxygenase inhibitor, however, partially restored the relaxation to K⁺, impaired in the presence of arachidonic acid (30 ¦ÌM). On the other hand, cyclooxygenase inhibitor indomethacin failed to reverse the inhibitory effect of arachidonic acid on KCl-induced relaxation. Staurosporin, 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.