Vasoconstrictor Effects of Iso-Prostaglandin F2α Type-III (8-Iso-Prostaglandin F2α) on Human Saphenous Veins

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Abstract
Free radical generation can initiate the peroxidation of arachidonic acid, resulting in a non-cyclooxygenase-dependent production of bioactive prostaglandin F2-like compounds. We have investigated the effects of iso-prostaglandin F2α type III, (iPF2α-III, formerly named 8-iso prostaglandin F2α) on human saphenous veins, and characterized the underlying mechanisms. In organ baths, the contractile effects of iPF2α-III were tested on saphenous vein rings coming from 22 patients. iPF2α-III induced concentration-dependent contractions of isolated human saphenous veins. The maximal contraction did not differ significantly from that of prostaglandin F2α (PGF2α). The pD2 values for iPF2α-III, PGF2α, endothelin-1 (ET-1), and U46619 (a stable thromboxane A2 mimetic) were 6.31 ± 0.12, 5.66 ± 0.13, 7.37 ± 0.08, and 7.99 ± 0.31, respectively (p < 0.001 for U46619 vs. iPF2α-III and PGF2α; and ET-1 vs. PGF2α). Emax values of iPF2α-III, PGF2α, ET-1, and U46619 were 137.7 ± 24.3%, 145.9 ± 7.5%, 92.9 ± 16.8%, and 238.7 ± 23.7%, respectively (p < 0.001 for U46619 vs. iPF2α-III, PGF2α and ET-1; and for PGF2α vs. ET-1). The responses to iPF2α-III were inhibited by GR 32191 10−7M, a TP-receptor antagonist, without affecting the maximal response (pD2 values were 5.98 ± 0.06 in the absence, and 5.22 ± 0.05 in the presence of GR32191; p < 0.001). Concentration-effect curves to iPF2α-III were not affected by phosphoramidon 10−5M (an endothelin converting enzyme inhibitor), BQ123 10−6M (a selective ETA-receptor antagonist), BQ788 10−6M (a selective ETB-receptor antagonist), and indomethacin 10−5M (a cyclooxygenase inhibitor). Finally, the contractile response of iPF2α-III did not involve the release of thromboxane B2 and ET-1, measured using enzyme immunoassays. This study demonstrates that iPF2α-III is a vasoconstrictor of human saphenous veins, with a potency fourfold greater than that of PGF2α, and 50 times less than that of the thromboxane A2 mimetic, U46619. These effects are mediated at least in part by TP-receptor stimulation, but do not involve thromboxane A2 or ET-1 release.