Objective To test binding affinities for, and inhibitory effects on, myometrium of some oxytocin and vasopressin antagonists with respect to their therapeutic potential.Design Receptor binding studies on transfected cell lines. In vifro contractility studies of human myometrium.Setting The Research Laboratory of Sanofi Recherche, Centre de Toulouse, France and the Departments of Obstetrics and Gynecology, Lund University Hospital, Sweden and Bialystok University Hospital, Poland.Participants Nine women delivered by caesarean section preterm and 37 delivered at term for routine obstetric indications. Results Oxytocin had a high affinity for the oxytocin receptor (K, in mean = 6.8 nmoYL) and bound, to some extent, to the vasopressin V,, receptor (K, = 34.9 nmol/L). Vasopressin displayed higher affinities for vasopressin V,,, V,, and V2 receptors (Ki = 1.4,0-8 and 4.2 nmovL, respectively) than for the oxytocin receptor (Ki = 48 nmoliL). Atosiban and SR 49059 both had a high affinity for the vasopressin V,, receptor (Ki = 4.7 and 7.2 nmoVL, respectively, and a moderate one for the oxytocin receptor (Ki = 397 and 340 nmoVL, respectively). SR 121463 exerted a predominant binding to the V, receptor (K, = 3-0 nmoVL). In the concentration-response experiments levels of up to 10 nmol/L of SR 49059 had no influence on the effect of oxytocin on myometrium from women preterm and at term pregnancy. However, a concentration-dependent inhibition of the responses of both these type of tissues to vasopressin was seen. The effects of EC,o concentrations of oxytocin and vasopressin on term pregnant myometrium were markedly inhibited by 10 nmovL and higher concentrations of SR 49059, the inhibition of the response to vasopressin being more pronounced than that of the oxytocin response. SR 121463 at maximal concentration only caused slight inhibitions of the oxytocin and vasopressin responses. InterventionsConclusions Atosiban and SR 49059 both have moderate binding affinities for the human oxytocin receptor and high binding affinities for the vasopressin V,, one. We demonstrated that SR 49059 inhibits the response of term myometrium to oxytocin and that of both preterm and term myometrium to vasopressin. These observations suggest a therapeutic potential of SR 49059 in preterm labour. The vasopressin V, receptor is apparently not involved to any significant degree in the activation of the pregnant human uterus.

Objective To study in nonpregnant women myometrial actions of vasopressin and oxytocin and Subjects Twenty-eight women undergoing hysterectomy for benign gynaecological disorders. Interventions Intrauterine pressure recordings. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin and oxytocin. Repeated blood sampling for measurement of vasopressin and oxytocin concentrations in plasma. Recording of effects of vasopressin and oxytocin on isolated myometrium. Estimation of myometrial concentrations of vasopressin V 1 a and oxytocin receptors. Measurement of plasma oestradiol and progesterone. Main outcome measures Vasopressin-and oxytocin-induced increases of the area under the in vivo recording curve over 10 minutes and EC,, concentrations of dose-responses in vitro. Concentrations of vasopressin Vla and oxytocin receptors. ResultsVasopressin was on average four times more potent than oxytocin in vivo. The effect of vasopressin premenstrually was more pronounced than in women under oestrogen influence only (proliferative phase-hyperproliferation; P = 0.02), and tended to be more marked than in those in the luteal phase (P = 0.07). No significant variation in oxytocin response with the hormonal state was observed. EC,, concentrations of vasopressin were more than 20 times lower than those of oxytocin. The median concentration of the vasopressin Vla receptor was 208 (range 139-343) fmol/mg protein and that of the oxytocin receptor 49 (38-87) fmol/mg protein. Vasopressin receptor concentrations and in vivo effects of this peptide did not correlate, whereas for those of oxytocin a significant correlation was observed (P = 0.02). ConclusionThe high potency of vasopressin in nonpregnant women, particularly premenstrually, firmly supports an aetiological importance of this peptide in the uterine hyperactivity of primary dysmenorrhoea. Oxytocin seems to be less important in this condition in view of its much smaller potency and the absence of increase in effect premenstrually. Vasopressin appears to influence both the oxytocin and the vasopressin Vla receptor sites in the uterus, whereas oxytocin acts specifically on its own receptor.

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Elevated Cd and Pb concentrations in the blood and placenta of pregnant women may be connected with the occurrence of miscarriage; therefore, the levels of these heavy metals should be monitored in women who plan pregnancy. It seems that determining the level of molar ratio between toxic metal and antioxidant elements can be analyzed as a marker for selection for control examinations as a valuable complement to existing diagnostic procedures in prevention, especially in early pregnancy. Additional diagnostic methods should be established as new tools in perinatal care in order to enable early diagnosis of pregnancy pathology and, especially, to prevent miscarriage.

Objective To study aspects of the aetiology of primary dysmenorrhoea and mechanisms underlying the therapeutic effect in this condition of an oral contraceptive. Intervention Intrauterine pressure was recorded before and during infusion of hypertonic saline (5% NaCl, 0.06 ml/kg/min) over 75 min on the first day of bleeding in women with dysmenorrhoea and after 3 weeks of oral contraceptive treatment. Plasma sampling every 15 min of ongoing infusion for the estimation of osmolality, arginine vasopressin, oxytocin and the prostaglandin (PG) F‐metabolito, 15‐keto‐13, 14‐dihydro‐PGF2α. Subjects Ten healthy nulliparous women with moderate to severe primary dysmenorrhoea. Main outcome measures Plasma levels of posterior pituitary hormones and the PGF‐metabolite. Total pressure area (TPA) of the recording curve. Results In dysmenorrhoea before infusion the plasma concentration of vasopressin was in mean 2.18, oxytocin 5.05 and the PGF‐metabolite 321.5 pmol/1, and the TPA 3.8 kPa ≥ 10 min. After oral contraceptive treatment the vasopressin level and the TPA were significantly reduced. At both sessions apart from intensifying the pain, the saline infusion increased vasopressin and oxytocin levels as well as the TPA, whereas the concentration of the PGF‐metabolite at both sessions decreased. Conclusion Confirmation is provided of the elevated secretion of arginine vasopressin and PGF2α, as well as increased uterine activity in primary dysmenorrhoea. The observations are in agreement with the concept that a lowered level of vasopressin and a decreased uterine activity contributes to the beneficial effect of OCs in the condition. Stimulation of the secretion of vasopressin increases the uterine activity and symptoms of primary dysmenorrhoea, but results suggest that this effect does not involve a mechanism of increased PGF‐synthesis. The role of oxytocin in dysmenorrhoea can not yet be defined.