Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study.

BACKGROUND: The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ). METHODS: Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines. RESULTS: BPJ (2.5 µg/mL), atosiban (0.27 µg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability. CONCLUSIONS: BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

Comparación del efecto tocolítico, in vitro, entre un anticálcico(Nifedipina) versus un B- agonista(Terbutalina) en útero de rata: estudio descriptivo. Informe preliminar

En útero de rata, previamente estrogenizado, se comparó el efecto tocolítico, nanomol(dosis de contracción 50, previamente titulada en nuestro laboratorio), alternadas con seis diferentes infusiones de tres nanomoles de terbutalina y tres nanomoles de Nifedipina. Se encontró que utilizando la misma dosis de ambos fármacos, existe un mayor efecto tocilítico(disminución del número de contracciones uterinas por minuto) con la Nifedipina que con la Terburtalina. La Nifedipina a pesar de nuevas infusiones de oxitocina, presentó un efecto tocolítico sostenido, no sucediendo lo mismo con la Terbutalina

Inhibition of the tocolytic activity of atrial natriuretic factor by progesterone and potentiation by progesterone receptor antagonist RU486 in rats.

1. The influence of progesterone on the activity of atrial natriuretic factor (ANF) on rat myometrial motor activity was determined in vitro. 2. ANF inhibited the tension development by myometrium from cycling or oestrogen-treated rats in a dose-dependent manner; maximal inhibition was 100%. 3. Injections of progesterone into rats inhibited the tocolytic activity of ANF in a dose and time-dependent manner. The tocolytic effects of ANF were completely abolished by 3 daily injections of 1 mg kg-1 progesterone. 4. Pregnancy-related increase in plasma progesterone was accompanied by a corresponding decrease in the tocolytic effects of ANF; myometria from gestational day 10 to 21 were completely refractory and those from earlier gestational age and immediate postpartum were responsive to ANF to varying degrees. 5. Treatment of pregnant rats with the progesterone antagonist, RU486, caused abortions and vaginal bleeding, decreased plasma progesterone concentrations and restored the tocolytic activity of ANF. Tocolytic activity of ANF on virgin rat myometria was potentiated by RU486. 6. Progesterone also inhibited the effects of ANF on myometria from ovariectomized rats. 7. Tocolytic activity of isoprenaline was not modified by progesterone, pregnancy, RU486 or ovariectomy. 8. It is concluded that progesterone antagonizes myometrial effects of ANF by an oestrogen-independent mechanism and the pregnancy-induced refractoriness to the tocolytic effects of ANF is caused by progesterone.