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.
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 omega-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not modulate 5-HT-initiated contractions at either level of PO2. (iii) alpha-Methyl-5-hydroxytryptamine (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 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 microM) significantly inhibited 5-HT- and ET-1-mediated contractions.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, AB, Canada.
Triggle
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D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009543:Nifedipine / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015398:Signal Transduction; D014469:Umbilical Arteries / Q000187:drug effects*
D016232:Endothelins; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D001120:Arginine; D009543:Nifedipine; D011188:Potassium; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester