Inhibition of the oxygen-induced contraction of the isolated human umbilical artery by indomethacin, flurbiprofen, aspirin and drugs modifying Ca2+ disposition.
In this study we have quantified the potency of three cyclo-oxygenase inhibitors, indomethacin, flurbiprofen and aspirin to reduce the vasoconstriction of isolated strips of human umbilical artery (HUA) to changing the oxygen-tension (PO2) of the bathing medium. The inhibitory potencies (IC50) of indomethacin and flurbiprofen were similar (IC50 = 2.1 x 10(-9) M and 7.6 x 10(-9) M respectively) while aspirin (IC50 = 2.5 x 10(-5) M) was approximately 12,000 fold less potent than indomethacin. At the physiological PO2 of 15 mmHg the isolated HUA was found to have an inherent cyclo-oxygenase induced tone since either reducing the PO2 from 15 to OmmHg or adding cyclo-oxygenase inhibitors caused vasorelaxation. O2-induced contractions were partly dependent on extracellular Ca2+: nifedipine and Bay K 8644 inhibited and enhanced oxygen-induced contractions, respectively, but did not have a significant effect on calcium-dependent 5-hydroxy-tryptamine-induced (5-HT) contractions. Therefore cyclo-oxygenase products and 5-hydroxytryptamine-induced contractions of the HUA may both utilise extracellular calcium but through different processes.
MacLennan
S J
SJ
Autonomic Physiology Unit, The University, Glasgow, Schotland.
McGrath
J C
JC
Whittle
M J
MJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010313:Partial Pressure; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology*; D012016:Reference Values; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology
D011422:Propionates; D009599:Nitroprusside; D005480:Flurbiprofen; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D001241:Aspirin; D010100:Oxygen; D002118:Calcium; D007213:Indomethacin