The effects of alpha-methyldopa on myometrial noradrenaline release and myometrial contractility in rat.
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.
Csonka
Dénes
D
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Zupkó
István
I
Minorics
Renáta
R
Márki
Arpád
A
Csík
Gábor
G
Falkay
George
G
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008750:Methyldopa / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014590:Uterine Contraction / Q000187:drug effects*
D013565:Sympatholytics; D008750:Methyldopa; D009638:Norepinephrine