Vasoconstrictor effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F(2alpha) on human umbilical vein.
The present study was undertaken to determine whether 8-iso-prostaglandin E2 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 E2 or 8-iso-prostaglandin F(2alpha) were constructed. Both isoprostanes evoked concentration-dependent contraction. 8-iso-prostaglandin E2 (pEC50=6.90+/-0.03) was significantly more potent than 8-iso-prostaglandin F(2alpha) (pEC50=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,2alpha(Z),3alpha,4alpha)]-5-Heptenoic acid) produced a competitive rightward shift of 8-iso-prostaglandin E2 concentration-response curves with pKB 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 pA2 values of 9.02+/-0.12 and 8.26+/-0.13, respectively. In conclusion, the present study describes for the first time the vasoconstrictor action of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F(2alpha) in human umbilical vein. Furthermore, the affinity values obtained with ICI-192,605 and SQ-29548 provide strong pharmacological evidence of prostanoid TP receptors involvement in this effect.
Daray
Federico M
FM
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 9, 1121, Buenos Aires, Argentina.
Minvielle
Ana I
AI
Puppo
Soledad
S
Rothlin
Rodolfo P
RP
D019086:Bridged Bicyclo Compounds, Heterocyclic; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D028421:Isoprostanes / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D014471:Umbilical Veins / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D028421:Isoprostanes; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C057498:ICI 192605; C075750:8-epi-prostaglandin F2alpha; C045749:SQ 29548; D015237:Dinoprost; D015232:Dinoprostone; C011987:8-isoprostaglandin E2