The cyclo-oxygenase-dependent regulation of rabbit vein contraction: evidence for a prostaglandin E2-mediated relaxation.
1. Arachidonic acid (0.01-1 microM) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentrations higher than 1 microM. Concentrations higher than 1 microM were required to induce dose-dependent contraction of vena cava and thoracic aorta from the same animals. 2. Pretreatment with a TP receptor antagonist (GR32191B or SQ29548, 3 microM) 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. 3. 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 (10 microM) pretreatment. 4. In the saphenous vein, PGE2 was respectively a 50 and 100 fold more potent relaxant prostaglandin than PGI2 and PGD2. Pretreatment with the EP4 receptor antagonist, AH23848B, shifted the concentration-relaxation curves of this tissue to arachidonic acid in a dose-dependent manner. 5. In the presence of 1 microM arachidonic acid, venous rings produced 8-10 fold more PGE2 than did aorta whereas 6keto-PGF1alpha and TXB2 productions remained comparable. 6. Intact rings of saphenous vein relaxed in response to A23187. Pretreatment with L-NAME (100 microM) or indomethacin (10 microM) 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. 7. We conclude that stimulation of the cyclo-oxygenase pathway by arachidonic acid induced endothelium-dependent, PGE2/EP4 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 PGE2.
Laboratoire INNOTHERA, Service de Pharmacologie, Arcueil, France.
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Rouaud
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Delaforge
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Anger-Leroy
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Le Filliatre
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Finet
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Hanf
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016718:Arachidonic Acid / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D013931:Thromboxanes / Q000378:metabolism; D014684:Venae Cavae / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D006538:Heptanoic Acids; D007476:Ionophores; D011448:Prostaglandin Antagonists; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D016718:Arachidonic Acid; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; C046926:AH 23848; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; C060013:vapiprost; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin