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Differential reactivity of human mammary artery and saphenous vein to prostaglandin E 2 : Implication for cardiovascular grafts
Author(s) -
Foudi N,
Kotelevets L,
Gomez I,
Louedec L,
Longrois D,
Chastre E,
Norel X
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01264.x
Subject(s) - vasodilation , vasoconstriction , agonist , context (archaeology) , medicine , artery , prostaglandin e , endocrinology , immunostaining , receptor , coronary artery bypass surgery , prostaglandin , blood vessel , immunohistochemistry , biology , paleontology
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.