BACKGROUND: alpha-Methyldopa is a classic antihypertensive agent, used routinely in the treatment of pregnancy-induced hypertension. However, only a few data are available about its direct uterotropic effect. Accordingly, the aim of the present study was to investigate the direct effects of alpha-methyldopa on the myometrial adrenergic functions in rat.
METHODS: The effects of alpha-methyldopa on the sympathetic transmission in the non-pregnant, early pregnant and late-pregnant myometrium were investigated by a superfusion technique. Myometrial samples from control and alpha-methyldopa-treated (200 mg/kg i.p. for 7 days) non-pregnant, 7-day and 21-day pregnant rats were saturated with [(3)H]noradrenaline, and the liberation evoked by electric field stimulation was determined. The contractility responses to alpha- and beta-adrenergic stimulation were additionally characterised by generating concentration-response curves of myometrial rings to noradrenaline and terbutaline in the same arrangement. The changes in the density and affinity of the adrenergic receptors (alpha(2) and beta(2)) were investigated by a radioligand binding technique.
RESULTS: The treatment with alpha-methyldopa substantially decreased both the [(3)H]noradrenaline uptake and release in both the non-pregnant and early pregnant uterus, while treatment-dependent changes were observed at term only in the uptake capacity. The contractility response to exogenous alpha-sympathomimetics was higher in the group treated in early pregnancy, and a decreased terbutaline-induced relaxation was observed in the non-pregnant state and at term. The treatment resulted in increased affinity for alpha(2) receptors in early pregnancy, while K(d) for beta(2) was increased at term.
CONCLUSIONS: Our experimental data suggest that besides its antihypertensive effect, alpha-methyldopa may influence the adrenergic transmission of the pregnant uterus. Our results indicate that the agent decreases the efficacy of beta(2)-adrenergic agonists at term pregnancy and increases the response to alpha-sympathomimetics in early pregnancy.
