Vasoconstrictor effects of iso-prostaglandin F2alpha type-III (8-iso-prostaglandin F2alpha) on human saphenous veins
Gardan, B.; Cracowski, J.L.; Sessa, C.; Hunt, M.; Stanke-Labesque, F.; Devillier, P.; Bessard, G.
Journal of Cardiovascular Pharmacology 35(5): 729-734
2000
ISSN/ISBN: 0160-2446 PMID: 10813374 Document Number: 516863
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 F2alpha type III, (iPF2alpha-III, formerly named 8-iso prostaglandin F2alpha) on human saphenous veins, and characterized the underlying mechanisms. In organ baths, the contractile effects of iPF2alpha-III were tested on saphenous vein rings coming from 22 patients. iPF2alpha-III induced concentration-dependent contractions of isolated human saphenous veins. The maximal contraction did not differ significantly from that of prostaglandin F2alpha (PGF2alpha). The pD2 values for iPF2alpha-III, PGF2alpha, 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. iPF2alpha-III and PGF2alpha; and ET-1 vs. PGF2alpha). Emax values of iPF2alpha-III, PGF2alpha, 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. iPF2alpha-III, PGF2alpha and ET-1; and for PGF2alpha vs. ET-1). The responses to iPF2alpha-III were inhibited by GR 32191 10-7 M, 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 iPF2alpha-III were not affected by phosphoramidon 10-5 M (an endothelin converting enzyme inhibitor), BQ123 10-6 M (a selective ETA-receptor antagonist), BQ788 10-6 M (a selective ETB-receptor antagonist), and indomethacin 10-5 M (a cyclooxygenase inhibitor). Finally, the contractile response of iPF2alpha-III did not involve the release of thromboxane B2 and ET-1, measured using enzyme immunoassays. This study demonstrates that iPF2alpha-III is a vasoconstrictor of human saphenous veins, with a potency fourfold greater than that of PGF2alpha, 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.