TY - JOUR
T1 - The cyclo-oxygenase-dependent regulation of rabbit vein contraction
T2 - Evidence for a prostaglandin E2-mediated relaxation
AU - Kingma, Idsart
AU - Toussaint, Huub M.
AU - Commissaris, Dianne A.C.M.
AU - Savelsbergh, Geert J.P.
PY - 1999/1/27
Y1 - 1999/1/27
N2 - 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.
AB - 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.
KW - A23187
KW - Arachidonic acid
KW - Relaxation
KW - Saphenous vein
KW - Vena cava
UR - http://www.scopus.com/inward/record.url?scp=0032893045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032893045&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0702265
DO - 10.1038/sj.bjp.0702265
M3 - Article
C2 - 10051118
AN - SCOPUS:0032893045
SN - 0007-1188
VL - 126
SP - 35
EP - 44
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 1
ER -