Vasoconstrictor effects of iso-prostaglandin F-2 alpha type-III (8-iso-prostaglandin F-2 alpha) on human saphenous veins

Free radical generation can Initiate the peroxidation of arachidonic acid. resulting in a non-cyclooxygenase-dependent production of bioactive prostag landin F-2-like compounds. We have investigated the effects of iso-prostagl andin F-2 alpha type III, (iPF(2 alpha)-In, formerly named 8-iso prostaglan din F-2 alpha) on human saphenous veins, and characterized the underlying m echanisms. In organ baths, the contractile effects of iPF(2 alpha)-III were tested on saphenous vein rings coming from 22 patients. iPF(2 alpha)-III i nduced concentration-dependent contractions of isolated human saphenous vei ns. The maximal contraction did not differ significantly from that of prost aglandin F-2 alpha (PGF(2 alpha)). The pD(2) values for iPF(2 alpha)-III, P GF(2 alpha), endothelin-l (ET-1), and U46619 (a stable thromboxane A(2) mim etic) 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. iPF(2 alpha)-III and PGF(2 alpha): a nd ET-1 vs. PGF(2 alpha)). E-max values of iPF(2 alpha)-III, PGF(2 alpha), ET-1, and U46619 were 137.7 +/- 24.3%, 145.9 +/- 7.5%, 92.9 +/- 16.8%, and 738.7 +/- 23.7%, respectively (p < 0.001 for U46619 vs. iPF(2 alpha)-III, P GF(2 alpha) and ET-1, and for PGF(2 alpha) vs. ET-1). The responses to iPF( 2 alpha)-III were inhibited by GR 32191 10(-7) M, a TP-receptor antagonist, without affecting the maximal response (pD(2) values were 5.98 +/- 0.06 in the absence, and 5.22 +/- 0.05 in the presence of GR32191; p < 0.001). Con centration-effect curves to iPF(2 alpha)-III were not affected by phosphora midon 10(-5) M tan endothelin converting enzyme inhibitor), BQ123 10(-6) M (a selective ETA-receptor antagonist), BQ788 10(-6) M (a selective ETB-rece ptor antagonist), and indomethacin 10-5 M (a cyclooxygenase inhibitor). Fin ally, the contractile response of iPF(2 alpha)-III did not involve the rele ase of thromboxane B-2 and ET-1, measured using enzyme immunoassays. This s tudy demonstrates that iPF(2 alpha)-III is a vasoconstrictor of human saphe nous veins, with a potency fourfold greater than that of PGF(2 alpha) and 5 0 times less than that of the thromboxane A(2) mimetic, U46619. These effec ts are mediated at least in part by TP-receptor stimulation, but do not inv olve thromboxane A(2) or ET-I release.