Sodium pump activation by 5-hydroxytryptamine in human placental veins

The aim of the present study was to determine the influence of the sodium pump on the responses elicited by 5-hydroxytryptamine (5-HT) in segments of human placental veins. 5-HT (10(-9)-3 x 10(-7) M) elicited potent concentration-dependent vasoconstrictor responses, but a fall in tone was observed at higher concentrations. In the presence of 10(-7) M ouabain, this fall in tension was abolished. A single concentration of 5-HT (10(-6) M) produced a biphasic response, consisting in a fast early contraction followed by a slow relaxation. This relaxant phase was concentration dependently inhibited by ouabain (10(-7) and 10(-6) M), and abolished by preincubating the vessels in a K(+)-free solution and reducing bath temperature to 28 degrees C, methods usually employed to inhibit the sodium pump. After adding 7.5 mM K+ or returning the temperature to 37 degrees C, marked relaxation was observed. On the other hand, the relaxant phase with the amine remained unchanged by pretreatment with phenidone, oxyhemoglobin, indomethacin (all at 10(-5) M) and endothelium removal. 5-HT (10(-7) and 10(-6) M) elicited increases in ouabain-sensitive 86Rb+ uptake. These results suggest that: (1) 5-HT activates Na+,K(+)-ATPase, likely by an indirect mechanism that involves an increase of intracellular sodium concentration; and (2) the relaxant phase of 5-HT-evoked vasoactive responses is not mediated by the release of nitric oxide or prostacyclin from the endothelium.