Actions of 8-Epi prostaglandin F2α on isolated rat aorta

8-Epi prostaglandin F-2 alpha (8-epi PGF(2 alpha)) contracted rat thoracic aorta rings in a concentration-dependent manner in the presence or absence of functional endothelium [median effective concentration (EC50) values, 455 +/- 52 and 268 +/- 34 nM, respectively; Student's t test; p = 0.006]. U46619 was a more potent agonist with or without functional endothelium (EC50 values, 6.8 +/- 1.6 and 4.5 +/- 1.0 nM, respectively). SQ29548 [a thromboxane (TP)-receptor antagonist] inhibited contractions to both 8-epi PGF(2 alpha) and U46619 in a competitive manner, with mean pA(2) values of 8.3 and 7.9, respectively. 8-Epi PGF(2 alpha) had a further contractile effect in vessels that had been contracted with noradrenaline and had been shown to possess a functional endothelium. Inhibition of thromboxane synthesis with OKY-046 or blockade of endothelin receptors with bosentan had no effect on responses to 8-epi PGF(2 alpha) or U46619. Preincubation with 8-epi PGF(2 alpha) or noradrenaline shifted the concentration-response curves to U46619 upward at low concentrations of U46619 with no significant change in EC50 Values or maximal responses. Reduction of TP-receptor number in rat aorta with dithiothreitol caused a concentration-dependent inhibition of responses to both U46619 and 8-epi PGF(2 alpha), with no effect on maximal responses and or on the responses to U46619 after the preincubation with 8-epi PGF(2 alpha). These results indicate that 8-epi PGF(2 alpha) is a potent vasoconstrictor in the rat aorta and are suggestive of an action of 8-epi PGF(2 alpha) at the TP receptor.