Isoprostaglandin E2 type-III (8-iso-prostaglandin E2) evoked contractions in the human internal mammary artery.
E2-isoprostanes are recently discovered compounds that are produced in vivo from free radical-catalysed peroxidation of arachidonic acid. One such compound whose formation is favoured by this mechanism is isoprostaglandin E2 type III (iPE2-III, also named 8-iso-prostaglandin E2 or 15-E2t-isoprostaglandin). The aim of this study was to evaluate the vasomotor properties of iPE2-III in isolated human internal mammary artery. In organ bath, iPE2-III was approximately 10 times more potent than isoprostaglandin F2alpha-III and 27 times more potent than prostaglandin E2, whereas both isoprostaglandin F3alpha-III and 15-epi-isoprostaglandin F2alpha-II induced weak contractions. The responses to iPE2-III were inhibited in a concentration-dependent manner by the thromboxane A2 receptor antagonist GR 32191 (3.10(-9) to 3.10(-7) M). Indomethacin, a cyclooxygenase inhibitor and phosphoramidon, an endothelin converting enzyme inhibitor, did not affect iPE2-III response. These data shows that iPE2-III is a more potent vasoconstrictor of human internal mammary arteries than isoprostaglandin F2alpha-III. These effects are mediated by TP receptors, but involve neither cyclooxygenase products nor endothelins. iPE2-III production may induce more pronounced vasomotor effects than isoprostaglandin F2alpha-III in situations of oxidative stress, and in particular may modulate internal mammary artery tone following coronary bypass surgery.
Cracowski
J L
JL
Laboratory of Pharmacology, LSCPA EA2937, Faculté de Médecine de Grenoble, La Tronche, France. Jean-Luc.Cracowski@ujf-grenoble.fr
Devillier
P
P
Chavanon
O
O
Sietchiping-Nzepa
F A
FA
Stanke-Labesque
F
F
Bessard
G
G
D000368:Aged; D001713:Biphenyl Compounds / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D028421:Isoprostanes; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009924:Organ Culture Techniques; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001713:Biphenyl Compounds; D028441:F2-Isoprostanes; D006020:Glycopeptides; D006538:Heptanoic Acids; D028421:Isoprostanes; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C060013:vapiprost; D015232:Dinoprostone; C008890:phosphoramidon; C011987:8-isoprostaglandin E2; D007213:Indomethacin