Characterization of NPY receptors mediating contraction in rat intramyocardial coronary arteries

Abstract

In vitro experiments in a microvascular myograph were designed in order to characterize the receptor subtypes and the mechanisms underlying the contractions induced by neuropeptide Y (NPY) in rat coronary small arteries. The rank order of potency for NPY-receptor agonist-induced increases in tension in endothelium-intact preparations was polypeptide Y (PYY)>NPY≥[Leu 31Pro 34]NPY, while NPY 13–36 only induced small contractions at the highest concentration applied. The selective neuropeptide Y 1 receptor antagonist, BIBP 3226, caused rightward shifts in the concentration–response curves for NPY and the slope of the Schild plot was not significantly different from unity. The p A 2 value for BIBP 3226 against NPY was 7.88±0.15 ( n=6). We have earlier shown that endothelial cell removal does not change the contractile responses induced by NPY, but indomethacin (3×10 −6 M) significantly reduced the contractions induced by the peptide. In contrast, the thromboxane receptor antagonist, SQ29548, which abolished the contractions induced by the thromboxane analogue, U46619, did not change the concentration–response curves for NPY. In conclusion, the present study suggests that Y 1 receptors mediate NPY-induced contractions in rat coronary resistance arteries, and that a non-thromboxane prostanoid is involved in the contractile mechanism.