A progressive increase in plasma levels of serotonin (5-HT) during pregnancy has been reported. Furthermore, an increase in the concentration of noradrenaline (NA) has been described during labor. On the other hand, in different arteries it has been observed that minimal effective concentrations of 5-HT are able to produce an increase or "amplification" of the contractile response to a second agonist. From these reports, it seemed interesting to determine the existence of a synergistic interaction between 5-HT and NA in the human umbilical artery (HUA), and the probable mechanisms involved. Therefore, strips of HUA were incubated in Krebs solution at 37 degrees C and gassed with a mixture of CO2 (5%) and O2 (95%). The contractile isometric response was assessed. After a period of two hours, complete cumulative concentration-response curves to 5-HT and to NA were obtained. The maximal contractile response to NA was approximately 20% of the maximal response to 5-HT. In another series of experiments, the response to NA was enhanced by previous treatment with minimal effective doses of 5-HT (control response 0.24 +/- 0.06 g; "amplified" response 0.53 +/- 0.06 g, P < 0.01). This "amplified" response to NA was correlated with the degree of previous contraction with 5-HT, when the last was between 3 and 30% of the maximal response. However, precontractions higher than 40% abolished the responses to NA. In other experiments, the artery strips were incubated during thirty minutes with diltiazem 1 microM before agonists addition. In this condition, a decrease in the control and amplified response was observed. Therefore, we have shown the existence of an amplifying effect of 5-HT over the response to NA in the HUA, and we discuss the possible mechanisms involved and the possible clinical relevance in preeclampsia.