THE ENDOTHELIUM CONTRIBUTES TO THE CONTRACTILE RESPONSES OF THE HUMANUMBILICAL ARTERY TO 5-HYDROXYTRYPTAMINE AND ENDOTHELIN-1 UNDER LOW BUT NOT HIGH PO-2 CONDITIONS

To determine the influences of both Po-2 and the presence of the endot helium on contractile responses of the human umbilical artery (HUA), t he effects of a series of vasoconstrictors were compared in ring prepa rations with and without endothelium at low (2.5% O-2, PO2, < 55 mmHg (1 mmHg = 133.3 Pa)) and high PO2 (95% O-2, PO2 > 600 mmHg). The resul ts demonstrate the following. (i) 5-Hydroxytryptamine (5-HT) and endot helin-1 (ET-1) contracted the HUA at either low or high PO2. At low PO 2, removal of the endothelium significantly reduced receptor-mediated responses. (ii) The nitric oxide synthase inhibitor N-omega-nitro-L-ar ginine methyl ester (L-NAME, 100 mu M) did not modulate 5-HT-initiated contractions at either level of PO2. (iii) alpha-Methyl-5-hydroxytryp tamine (alpha-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 l ow PO2 but unaffected by removal of the endothelium. (iv) Responses of the HUA to high potassium (hK(+)) were unaffected by either changes i n PO2 or removal of the endothelium. (v) The 5-HT2 receptor antagonist ketanserin at low concentration (10 nM) inhibited contractile respons es to 5-HT in an apparently competitive manner. However, with 100 nM k etanserin and at low PO2, inhibition became noncompetitive. Removal of the endothelium did not influence the action of ketanserin. (vi) Rega rdless of PO2, the Ca2+ channel antagonist nifedipine (1 mu M) signifi cantly inhibited 5-HT- and ET-1-mediated contractions. Depletion of ex tracellular Ca2+ also greatly reduced 5-HT-induced contractions. We co nclude that, in the HUA, endothelial cells and changes in PO2, differe ntially modulate contractions initiated by 5-HT agonists and ET-1, pos sibly via the release of an endothelium-derived contracting factor (ED CF).