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-hydroxy-tryptamine (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 Rb-86+ 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.