The cyclo-oxygenase-dependent regulation of rabbit vein contraction: evidence for a prostaglandin E-2-mediated relaxation

1 Arachidonic acid (0.01-1 mu M) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentr ations higher than 1 mu M. Concentrations higher than 1 mu M were required to induce dose-dependent contraction of vena cava and thoracic aorta from t he same animals. 2 Pretreatment with a TP receptor antagonist (GR32191B or S429548, 3 mu M) potentiated the relaxant effect in the saphenous vein, revealed a vasorelax ant component in the vena cava response and did not affect the response of the aorta. 3 Removal of the endothelium from the venous rings, caused a 10 fold rightw ard shift in the concentration-relaxation curves to arachidonic acid. Wheth er or not the endothelium was present, the arachidonic acid-induced relaxat ions were prevented by indomethacin (10 mu M) pretreatment. 4 In the saphenous vein, PGE(2) was respectively a 50 and 100 fold more pot ent relaxant prostaglandin than PGI(2) and PGD(2). Pretreatment with the EP 4 receptor antagonist, AH23848B, shifted the concentration-relaxation curve s of this tissue to arachidonic acid in a dose-dependent manner. 5 In the presence of 1 mu M arachidonic acid, venous rings produced 8-10 fo ld more PGE(2) than did aorta whereas 6keto-PGF(1 alpha) and TXB2 productio ns remained comparable. 6 Intact rings of saphenous vein relaxed in response to A23187. Pretreatmen t with L-NAME (100 mu M) or indomethacin (10 mu M) reduced this response by 50% whereas concomitant pretreatment totally suppressed it. After endothel ium removal, the remaining relaxing response to A23187 was prevented by ind omethacin but not affected by L-NAME. 7 We conclude that stimulation of the cyclo-oxygenase pathway by arachidoni c acid induced endothelium-dependent, PGE(2)/EP4 mediated relaxation of the rabbit saphenous vein. This process might participate in the A23187-induce d relaxation of the saphenous vein and account for a relaxing component in the response of the vena cava to arachidonic acid. It was not observed in t horacic aorta because of the lack of a vasodilatory receptor and/or the poo rer ability of this tissue than veins to produce PGE(2).