Vasorelaxation induced by prostaglandin E2 in human pulmonary vein: role of the EP4 receptor subtype.

Background and purpose:PGE₂ has been shown to induce relaxations in precontracted human pulmonary venous preparations, while in pulmonary arteries this response was not observed. We investigated and characterized the prostanoid receptors which are activated by PGE₂ in the human pulmonary veins.Experimental approach:Human pulmonary arteries and veins were cut as rings and set up in organ baths in presence of a TP antagonist. A pharmacological study was performed using selective EP₁₋₄ ligands. The cellular localization of the EP₄ receptors by immunohistochemistry and their corresponding transcripts were also investigated in these vessels.Key results:PGE₂ and the EP₄ agonists (L-902688, ONO-AE1-329) induced potent vasodilatation of the human pulmonary vein, pEC₅₀ values: <7.22±0.20, 8.06±0.12 and 7.80±0.09, respectively. These relaxations were inhibited by the EP₄ antagonist GW627368X and not modified in presence of the DP antagonist L-877499. Higher concentrations (1 μM) of the EP₂ agonist ONO-AE1-259 induced relaxations of the veins. The EP₄ agonists had no effect on the precontracted arteries. Finally, the EP₁ antagonists ONO-8713 and SC-51322 potentiated the relaxation of the veins induced by PGE₂. EP₄ and EP₁ receptors were detected by immunohistochemistry in the veins but not in the arteries. EP₄ mRNA accumulation was also greater in the veins when compared with the arterial preparations.Conclusions and implications:Of the 4 EP receptor subtypes, smooth muscle cells in the human pulmonary vein express the EP₄ and EP₁ receptor subtypes. The relaxations induced by PGE₂ in this vessel result from the activation of the EP₄ receptor.British Journal of Pharmacology (2008) 154, 1631–1639; doi:10.1038/bjp.2008.214; published online 2 June 2008 [ABSTRACT FROM AUTHOR]