Inhibition of the oxygen-induced contraction of the isolated human umbilical artery by indomethacin, flurbiprofen, aspirin and drugs modifying Ca2+ disposition

Abstract

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.