The endothelium contributes to the contractile responses of the human umbilical artery to 5-hydroxytryptamine and endothelin-1 under low but not high conditions

Abstract

To determine the influences of both [Formula: see text] and the presence of the endothelium on contractile responses of the human umbilical artery (HUA), the effects of a series of vasoconstrictors were compared in ring preparations with and without endothelium at low (2.5% O2, [Formula: see text] (1 mmHg = 133.3 Pa)) and high [Formula: see text] (95% O2, [Formula: see text]). The results demonstrate the following. (i) 5-Hydroxytryptamine (5-HT) and endothelin-1 (ET-1) contracted the HUA at either low or high [Formula: see text]. At low [Formula: see text], removal of the endothelium significantly reduced receptor-mediated responses, (ii) The nitric oxide synthase inhibitor Nω–nitro-L-arginine methyl ester (L-NAME, 100 μM) did not modulate 5-HT-initiated contractions at either level of [Formula: see text]. (iii) α-Methyl-5-hydroxytryptamine (α-Me-5-HT) and 5-carboxamidotryptamine (5-CT), relatively selective 5-HT1C/5-HT2 and 5-HT1-like receptor agonists, respectively, elicited contractions in the HUA, and the responses were reduced at low [Formula: see text] but unaffected by removal of the endothelium, (iv) Responses of the HUA to high potassium (hK+) were unaffected by either changes in [Formula: see text] or removal of the endothelium, (v) The 5-HT2 receptor antagonist ketanserin at low concentration (10 nM) inhibited contractile responses to 5-HT in an apparently competitive manner. However, with 100 nM ketanserin and at low [Formula: see text], inhibition became noncompetitive. Removal of the endothelium did not influence the action of ketanserin. (vi) Regardless of [Formula: see text], the Ca2+ channel antagonist nifedipine (1 μM) significantly inhibited 5-HT- and ET-1-mediated contractions. Depletion of extracellular Ca2+ also greatly reduced 5-HT-induced contractions. We conclude that, in the HUA, endothelial cells and changes in [Formula: see text] differentially modulate contractions initiated by 5-HT agonists and ET-1, possibly via the release of an endothelium-derived contracting factor (EDCF).Key words: endothelium, contracting factors, vascular smooth muscle, oxygen tension.