Differential reactivity of human mammary artery and saphenous vein to prostaglandin E₂: Implication for cardiovascular grafts

Abstract

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 E2 (PGE2). In this context, the physiological response of these vascular grafts to PGE2 is highly relevant. The aim of this study was thus to characterize the PGE2 receptor subtypes (EP1, EP2, EP3 or EP4) 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 PGE2 induced contractions of IMA (Emax= 1.43 ± 0.20 g; pEC50= 7.50 ± 0.10); contractions were also observed with the EP3 receptor agonists, sulprostone, 17‐phenyl‐PGE2, misoprostol or ONO‐AE‐248. In contrast, PGE2 induced relaxation of the precontracted SV (Emax=–0.22 ± 0.02 g; pEC50= 7.14 ± 0.09), as did the EP4 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 PGE2 induced potent and opposite effects on the human vascular segments used for grafting, namely vasoconstriction of the IMA and vasodilatation of the SV via EP3 and EP4 receptors respectively. These observations suggest that EP3 and EP4 receptors could constitute therapeutic targets to increase vascular graft patency.

Inhibition of microsomal PGE synthase‐1 reduces human vascular tone by increasing PGI2: a safer alternative to COX‐2 inhibition

“…In contrast, these treatments augmented the contractile response to noradrenaline (Figures C and A) in IMA, which was much more sensitive to the PGI 2 analogue (Supporting Information Figure S5 and Table S2). As PGE 2 induces vasodilatation via EP 4 receptors in SV but not in IMA (Foudi et al, ), the effect of the EP 4 receptor antagonist on vascular tone was tested only in SV and no effect was found (Supporting Information Table S1).…”

“…PGE 2 controls the vascular tone by inducing contraction ( via EP 3 receptors) in internal mammary arteries (IMA) or relaxation ( via EP 4 receptors) in saphenous veins (SV) (Foudi et al, ). Three PGE synthase (PGES) isoforms specifically catalyse the final step of PGE 2 biosynthesis from PGH 2 .…”

Distinct Roles of Central and Peripheral Prostaglandin E2 and EP Subtypes in Blood Pressure Regulation

“…In rings of human internal mammary arteries, which are frequently used for coronary artery bypass graft surgery, PGE 2 induces vasoconstriction via EP 3 receptors. 26 This study suggests that EP 3 antagonism may offer a new therapeutic intervention to increase vascular graft patency. In addition, PGE 2 is shown to induce smooth muscle contraction in rat mesentery artery.…”

The role of perivascular adipose tissue in obesity‐induced vascular dysfunction

“…The anticontractile effect of human PVAT has been shown for the internal mammary artery (Gao et al, ; Malinowski et al, ; Foudi et al, ; Malinowski et al, ; Ozen et al, ), the saphenous vein (Ford et al, ; Dashwood et al, , ; Foudi et al, ; Ozen et al, ) and for small arteries (Aghamohammadzadeh et al, ; Greenstein et al, ; Virdis et al, ).…”