SEROTONIN AMPLIFYING ACTION ON NORADRENAL INE RESPONSE IN HUMAN UMBILICAL ARTERY

A progressive increase in plasma levels of serotonin (5-HT) during pre gnancy has been reported. Furthermore, an increase in the concentratio n of noradrenaline (NA) has been described during labor. On the other hand, in different arteries it has been observed that minimal effectiv e concentrations of 5-HT are able to produce an increase or <<amplific ation>> of the contractile response to a second agonist. From these re ports, it seemed interesting to determine the existence of a synergist ic 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 O-2 (95%). The contractile isometric response was asse ssed. After a period of two hours, complete cumulative concentration-r esponse curves to 5-HT and to NA were obtained. The maximal contractil e 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 resp onse 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% o f the maximal response, However, precontractions higher than 40% aboli shed the responses to NA. In other experiments, the artery strips were incubated during thirty minutes with diltiazem 1 mu M before agonists addition. In this condition, a decrease in the control and amplified response was observed. Therefore, we have shown the existence of an am plifying effect of 5-HT over the response to NA in the HUA, and we dis cuss the possible mechanisms involved and the possible clinical releva nce in preeclampsia.