The endothelium contributes to the contractile responses of the human umbilical artery to 5-hydroxytryptamine and endothelin-1 under low but not high PO2 conditions

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Abstract

To determine the influences of both PO2 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, PO2 < 55 mmHg (1 mmHg = 133.3 Pa)) and high PO2 (95% O2, PO2 > 600 mmHg). The results demonstrate the following. (i) 5-Hydroxytryptamine (5-HT) and endothelin-1 (ET-1) contracted the HUA at either low or high PO2. At low PO2, removal of the endothelium significantly reduced receptor-mediated responses. (ii) The nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME, 100 μM) did not modulate 5-HT-initiated contractions at either level of PO2. (iii) α-Methyl-5-hydroxytryptamine (α-Me-5-HT) and 5-carboxamidotryptamine (5-CT), relatively selective 5-HT(1C)/5-HT2 and 5-HT1-like receptor agonists, respectively, elicited contractions in the HUA, and the responses were reduced at low PO2 but unaffected by removal of the endothelium. (iv) Responses of the HUA to high potassium (hK+) were unaffected by either changes in PO2 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 PO2, inhibition became noncompetitive. Removal of the endothelium did not influence the action of ketanserin. (vi) Regardless of PO2, 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 PO2 differentially modulate contractions initiated by 5-HT agonists and ET-1, possibly via the release of an endothelium-derived contracting factor (EDCF).

Original languageEnglish
Pages (from-to)1171-1179
Number of pages9
JournalCanadian Journal of Physiology and Pharmacology
Volume72
Issue number10
Publication statusPublished - 1994
Externally publishedYes

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Keywords

  • Contracting factors
  • Endothelium
  • Oxygen tension
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Pharmacology
  • Physiology (medical)

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