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

作者：Singh Thakur Uttam^*; Choudhury Soumen; Panda Subhashree; Maruti Bhojane Somnath; Mishra Santosh Kumar

来源：Vascular Pharmacology, 2012, 56(1-2): 84-90.

DOI：10.1016/j.vph.2011.11.005

• Arachidonic acid
• Na+-K+-ATPase
• Sheep
• Pulmonary artery

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 mu M) 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 mu M)-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-HEfE, 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 mu M). 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 add 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.

• 出版日期2012-2