Prostaglandin E2 induced contraction of human intercostal arteries is mediated by the EP3 receptor

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)E2 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 PGE2 and the characterization of the PGE2 receptor subtypes (EP1, EP2, EP3 or EP4) 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. PGE2 induced the contraction of HICA (Emax = 7.28 ± 0.16 g; pEC50 value = 0.79 ± 0.18; n = 17); contractions were also observed with the EP3 receptor agonists, sulprostone, 17-phenyl-PGE2, misoprostol or ONO-AE-248. In conclusion, PGE2 induced vasoconstriction of HICA via EP3 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 EP3 mRNA. These observations suggest that in the context of perioperative inflammation, increased PGE2 concentrations could trigger vasoconstriction of HICA and possibly alter spinal vascularization.