Cytochrome P450-dependent arachidonic acid metabolites, 19- and 20-hydroxyeicosatetraenoic acids, enhance sodium-potassium ATPase activity in vascular smooth muscle.
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.
Department of Pharmacology, New York Medical College, Valhalla 10595.
B
B
Escalante
W C
WC
Sessa
J R
JR
Falck
P
P
Yadagiri
M L
ML
Schwartzman
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D012414:Rubidium Radioisotopes; D010042:Ouabain; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D007213:Indomethacin