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.