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

Arachidonic acid (0.01–1μ M ) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentrations higher than 1μ M . Concentrations higher than 1μ M were required to induce dose‐dependent contraction of vena cava and thoracic aorta from the same animals. Pretreatment with a TP receptor antagonist (GR32191B or SQ29548, 3μ M ) potentiated the relaxant effect in the saphenous vein, revealed a vasorelaxant component in the vena cava response and did not affect the response of the aorta. Removal of the endothelium from the venous rings, caused a 10 fold rightward shift in the concentration‐relaxation curves to arachidonic acid. Whether or not the endothelium was present, the arachidonic acid‐induced relaxations were prevented by indomethacin (10μ M ) pretreatment. In the saphenous vein, PGE 2 was respectively a 50 and 100 fold more potent relaxant prostaglandin than PGI 2 and PGD 2 . Pretreatment with the EP 4 receptor antagonist, AH23848B, shifted the concentration‐relaxation curves of this tissue to arachidonic acid in a dose‐dependent manner. In the presence of 1μ M arachidonic acid, venous rings produced 8–10 fold more PGE 2 than did aorta whereas 6keto‐PGF 1α and TXB 2 productions remained comparable. Intact rings of saphenous vein relaxed in response to A23187. Pretreatment with L ‐NAME (100μ M ) or indomethacin (10μ M ) reduced this response by 50% whereas concomitant pretreatment totally suppressed it. After endothelium removal, the remaining relaxing response to A23187 was prevented by indomethacin but not affected by L ‐NAME. We conclude that stimulation of the cyclo‐oxygenase pathway by arachidonic acid induced endothelium‐dependent, PGE 2 /EP 4 mediated relaxation of the rabbit saphenous vein. This process might participate in the A23187‐induced 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 thoracic aorta because of the lack of a vasodilatory receptor and/or the poorer ability of this tissue than veins to produce PGE 2 .British Journal of Pharmacology (1999) 126 , 35–44; doi: 10.1038/sj.bjp.0702265