Potentiation by neuropeptide Y of 5HT2A receptor-mediated contraction in porcine coronary artery

Potentiation by neuropeptide Y of serotonin (5-HT)-induced vasoconstriction was investigated in porcine coronary artery. 5-HT caused concentration-dependent contraction through 5-HT2A receptors. Neuropeptide Y (30 nM) significantly increased the 5HT-induced contraction by 16 +/- 5% in arteries with intact endothelium. Removal of the endothelium abolished the Potentiation. A neuropeptide Y-1 antagonist, BIBP3226, blocked this neuropeptide Y-induced potentiation. In vessels with intact endothelium, the potentiation by neuropeptide Y was inhibited by in the presence of a cyclo-oxygenase inhibitor, indomethacin (30 mu M), but not by the presence of ETA or ETB endothelin receptor antagonists or an NO synthase inhibitor, N-G-nitro-L-arginine (L-NNA) (1 mM) at all. A thromboxane A(2) (TXA(2)) synthase inhibitor, ozagrel, and prostanoid TP receptor antagonists, seratrodast and ONO-3708, also inhibited the neuropeptide Y-induced potentiation. In the endothelium-denuded arteries, a prostanoid TP receptor agonist, U-46619 (0.01 - 0.1 nM), potentiated 5-HT-induced contraction. These results indicate that neuropeptide Y potentiates the 5HT-induced contraction, due to release of TXA(2) from the endothelium via neuropeptide Y-1 receptors, in porcine coronary artery. (c) 2006 Elsevier B.V. All rights reserved.