The cyclo-oxygenase-dependent regulation of rabbit vein contraction: Evidence for a prostaglandin E2-mediated relaxation

Idsart Kingma, Huub M. Toussaint, Dianne A.C.M. Commissaris, Geert J.P. Savelsbergh

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

1. Arachidonic acid (0.01-1 μM) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentrations higher than 1 μM. Concentrations higher than 1 μM 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 μM) 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 μM) 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 μM arachidonic acid, venous rings produced 8-10 fold more PGE2 than did aorta whereas 6keto-PGF(1α) and TXB2 productions remained comparable. 6. Intact rings of saphenous vein relaxed in response to A23187. Pretreatment with L-NAME (100 μM) or indomethacin (10 μM) 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.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalBritish Journal of Pharmacology
Volume126
Issue number1
DOIs
Publication statusPublished - 27 Jan 1999

Keywords

  • A23187
  • Arachidonic acid
  • Relaxation
  • Saphenous vein
  • Vena cava

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