Isoprostaglandin E2 type-III (8-iso-prostaglandin E2) evoked contractions in the human internal mammary artery

E-2-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 E-2 type III (iPE(2)-III, also named 8-iso-prostaglandin E-2 or 15-E-2t-isoprostaglandin). The aim of this study was to evaluate the vasomotor properties of iPE(2)-III in isolated human internal mammary artery. In organ bath, iPE(2)-III was approximately 10 times more potent than isoprostaglandin F-2 alpha-III and 27 times more potent than prostaglandin E-2, whereas both isoprostaglandin F-3 alpha-III and 15-epi-isoprostaglandin F-2 alpha-III induced weak contractions. The responses to iPE(2)-III were inhibited in a concentration-dependent manner by the thromboxane Az 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 iPE(2)-III is a more potent vasoconstrictor of human internal mammary arteries than isoprostaglandin F-2 alpha-III. These effects are mediated by TP receptors, but involve neither cyclooxygenase products nor endothelins, iPE(2)-III production may induce more pronounced vasomotor effects than isoprostaglandin F-2 alpha-III in situations of oxidative stress, and in particular may modulate internal mammary artery tone following coronary bypass surgery. (C) 2001 Elsevier Science Inc. All rights reserved.