The authors investigate the effect of bumetan ide, an inhibitor of NKCC1 and a loop diuretic, on the tone of human umbilical artery (HUA). Rings of HUA (n = 35) from vaginal deliveries were suspended for isometric tension recordings in organ baths. Cumulative concentration-response curves to serotonin, histamine, and KCl were performed in the absence (control) or in the presence of bumetanide. The relaxant effect of bumetanide was also evaluated in serotonin- and histamine-induced contractions. Bumetanide inhibited HUA tone in serotonin- and histamine-induced contractions with significant changes in the potency (pD(2)) and maximum contractile response (E(max)) values. However, only pD( 2) values for KCl-induced contraction significantly changed in the presence of bumetanide. Bumetanide caused concentration-dependent and sustained relaxations in serotonin-induced contraction; however, there was refractoriness in histamine-induced contraction. These findings raise the possibility that NKCC1 may play a role in the regulation of the umbilical artery tone.