Cytochrome P450-Dependent Arachidonic Acid Metabolites, 19− and 20-Hydroxyeicosatetraenoic Acids, Enhance Sodium-Potassium ATPase Activity in Vascular Smooth Muscle

Abstract

Several cytochrome P450-dependent arachidonic acid metabolites have been shown to affect Na+,K(+)-ATPase activity. In the present study, we tested the effect of omega- and omega - 1-hydroxylated products, i.e., 19- and 20-hydroxyeicosatetraenoic acids (19- and 20-HETE), on the K-induced relaxation in rat aortic rings. 19-HETE and 20-HETE increased the magnitude of the potassium-induced relaxation in a dose-dependent fashion (10(-7)-10(-5) M). The inhibitory effect of ouabain on the potassium-induced relaxation was reversed by both 19- and 20-HETE. In addition, indomethacin fully inhibited the stimulatory effect of 19- and 20-HETE on relaxation induced by potassium. Vascular ouabain-sensitive 86Rb uptake was also increased by 19- and 20-HETE. These observations suggest that 19- and 20-HETE stimulate vascular Na+,K(+)-ATPase via their conversion by cyclooxygenase to prostaglandin-like material.