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Arterial vascularization of the spinal cord may be mechanically or functionally altered during thoraco-abdominal surgery/intravascular procedures. Increased arterial pressure has been shown to restore spinal perfusion and function probably by increasing the blood flow through the intercostal arteries. The regulation of human intercostal artery (HICA) vascular tone is not well documented. Prostaglandin (PG)E(2) concentration is increased during inflammatory conditions and has been shown to regulate vascular tone in many preparations. In this context, the pharmacological response of HICA to PGE(2) and the characterization of the PGE(2) receptor subtypes (EP(1), EP(2), EP(3) or EP(4)) involved are of importance and that is the aim of this study. Rings of HICA were prepared from 29 patients and suspended in organ baths for isometric recording of tension. Cumulative concentration-response curves were performed in these preparations with various EP receptor agonists in the absence or presence of different receptor antagonists or inhibitors. PGE(2) induced the contraction of HICA (E(max)=7.28 ± 0.16 g; pEC(50) value=0.79 ± 0.18; n=17); contractions were also observed with the EP(3) receptor agonists, sulprostone, 17-phenyl-PGE(2), misoprostol or ONO-AE-248. In conclusion, PGE(2) induced vasoconstriction of HICA via EP(3) receptor subtypes and this result was confirmed by the use of selective EP receptor antagonists (L-826266, ONO-8713, SC-51322) and by a strong detection of EP(3) mRNA. These observations suggest that in the context of perioperative inflammation, increased PGE(2) concentrations could trigger vasoconstriction of HICA and possibly alter spinal vascularization., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background and Purpose: Human internal mammary arteries (IMA) and saphenous veins (SV) are frequently used for coronary artery bypass graft surgery. Intra- and postoperatively, the bypass grafts are exposed to inflammatory conditions, under which there is a striking increase in the synthesis of prostaglandin E(2) (PGE(2) ). In this context, the physiological response of these vascular grafts to PGE(2) is highly relevant. The aim of this study was thus to characterize the PGE(2) receptor subtypes (EP(1) , EP(2) , EP(3) or EP(4) ) involved in modulation of the vascular tone in these two vessels., Experimental Approach: Rings of IMA and SV were prepared from 48 patients. The rings were mounted in organ baths for isometric recording of tension, and a pharmacological study was performed, together with associated reverse transcriptase PCR and immunohistochemistry experiments., Key Results: PGE(2) induced contractions of IMA (E(max) = 1.43 ± 0.20 g; pEC(50) = 7.50 ± 0.10); contractions were also observed with the EP(3) receptor agonists, sulprostone, 17-phenyl-PGE(2) , misoprostol or ONO-AE-248. In contrast, PGE(2) induced relaxation of the precontracted SV (E(max) =-0.22 ± 0.02 g; pEC(50) = 7.14 ± 0.09), as did the EP(4) receptor agonist, ONO-AE1-329. These results were confirmed by the use of selective EP receptor antagonists (GW627368X, L-826266, ONO-8713, SC-51322) and by molecular biology and immunostaining., Conclusions and Implications: PGE(2) induced potent and opposite effects on the human vascular segments used for grafting, namely vasoconstriction of the IMA and vasodilatation of the SV via EP(3) and EP(4) receptors respectively. These observations suggest that EP(3) and EP(4) receptors could constitute therapeutic targets to increase vascular graft patency., (British Journal of Pharmacology © 2011 The British Pharmacological Society. No claim to original French government works.)

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 EP(4) antagonist GW627368X and not modified in presence of the DP antagonist L-877499. Higher concentrations (>or=1 microM) of the EP2 agonist ONO-AE1-259 induced relaxations of the veins. The EP4 agonists had no effect on the precontracted arteries. Finally, the EP(1) 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.