Vasoconstrictor effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2α on human umbilical vein

The present study was undertaken to determine whether 8-iso-prostaglandin E-2 and 8-iso-prostaglandin F-2alpha posses contractile action on human umbilical vein and to evaluate the possible involvement of prostanoid TP receptors in this effect. Human umbilical vein rings were mounted in organ baths and concentration-response curves to 8-iso-prostaglandin E-2 or 8-iso-prostaglandin F-2alpha were constructed. Both isoprostanes evoked concentration-dependent contraction. 8-iso-prostaglandin E-2 (pEC(50)=6.90+/-0.03) was significantly more potent than 8-iso-prostaglandin F-2alpha (pEC(50)=6.10+/-0.04). However, both isoprostanes were equieffective. The prostanoid TP receptor antagonists, ICI-192,605 (4-(Z)-6-(2-o-Chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl)hexenoic acid) and SQ-29548 (7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-[1S(1alpha,alpha(Z),3alpha,4alpha)]-5-Heptenoic acid) produced a competitive rightward shift of 8-iso-prostaglandin E-2 concentration-response curves with pK(B) values of 8.91 +/- 0.04 and 8.07 +/- 0.07, respectively. When ICI-192,605 (1 nM) and SQ-29548 (10 nM) were evaluated against 8-iso-prostaglandin F-2alpha they produced a parallel rightward displacement of 8-iso-prostaglandin F-2alpha concentration-response curves without affecting the maximum responses giving pA(2) values of 9.02 +/- 0.12 and 8.26 +/- 0.13, respectively. In conclusion, the present study describes for the first time the vasoconsttictor action of 8-iso-prostaglandin E-2 and 8-iso-prostaglandin F-2alpha in human umbilical vein. Furthermore, the affinity values obtained with ICT-192,605 and SQ-29548 provide strong pharmacological evidence of prostanoid TP receptors involvement in this effect. (C) 2004 Elsevier B.V. All rights reserved.