Supersensitivity to the stimulant action of noradrenaline on human myometrium near term

Abstract

Noradrenaline (10-50 nM) and tyramine (0.05-1 mM) enhanced contractile force elicited by field stimulation of strips of myometrium from non-pregnant and pregnant women. In higher concentrations, noradrenaline produced sustained contractions. The EC50 values for noradrenaline were 0.4 microM in tissues from pregnant women and 3.1 microM in tissues from non-pregnant women; maximum responses were greater in the former tissues. In addition, the effects of noradrenaline on myometrium from pregnant women were more marked on the inner layer than on the outer layer, antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.1 and 1.0 microM), and unaffected by the inhibitor of neuronal uptake, nisoxetine (0.1 microM). Taken together, these observations confirm that supersensitivity to noradrenaline develops during pregnancy and is present near term. The supersensitivity to noradrenaline at term can be attributed only in part to a decrease in its removal by the sympathetic innervation, which declines towards term, because responses to tyramine were also enhanced in tissues from pregnant women. It is possible that gap junction formation may also contribute to this supersensitivity.