Aspirin and Indomethacin Prolong Parturition in Rats: Evidence that Prostaglandins Contribute to Expulsion of Foetus

Aiken, James W.

doi:10.1038/240021a0

Cited by 190 publications

(48 citation statements)

References 18 publications

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“…Since generation of prostaglandins can be initiated by mechanical stimuli such as touch or damage (Piper & Vane, 1971), the prostaglandin output from isolated uteri of pregnant rats could be a result of the stress of isolating the uterus, removing the contents and bathing it in an artificial salt solution. However, our in vitro findings were supported by the results of Aiken (1972) and Chester et al (1972) who found that indomethacin and similar drugs delayed and prolonged parturition in rats. They concluded that prostaglandin production by the uterus is necessary for foetal expulsion at term.…”

Section: Discussionsupporting

confidence: 81%

“…They concluded that prostaglandin production by the uterus is necessary for foetal expulsion at term. Further evidence for the participation of uterine prostaglandins in parturition was the dramatic increase in prostaglandin F2a production near term, at a time when the frequency of uterine contraction is known to increase; Aiken (1972) obtained similar results with uteri taken from rats during parturition. The endometrium appears to be the sole source of prostaglandins in the pregnant rat uterus (Williams, 1973) and the preliminary experiments of Challis, Harrison, Heap, Horton & Poyser (1972) indicate that prostaglandin output by the pregnant uterus of the sheep may be under hormonal control.…”

Section: Discussionsupporting

confidence: 70%

“…The increases in prostaglandin concentrations in human blood (Karim, 1968) and amniotic fluid (Karim & Devlin, 1967) during labour suggest that they may play a part in the expulsion of the uterine contents at parturition. Recent work by Aiken (1972) and Chester, Dukes, Slater & Walpole (1972) confirms this suggestion by showing that parturition is delayed -and prolonged in rats when prostaglandin production is prevented by prostaglandin synthetase inhibitors such as aspirin and indomethacin.…”

Section: Introductionsupporting

confidence: 53%

“…Thus, as in other isolated smooth muscles such as the cat iris (Posner, 1970), rabbit jejunum (Ferreira, Herman & Vane, 1972) rat stomach strip and guinea-pig colon (Eckenfels & Vane, 1972) a local prostaglandin production maintains the inherent smooth muscle activity. For the pregnant rat isolated uterus Aiken (1972) has come to a similar conclusion; he further showed that papaverine inhibits spontaneous activity without affecting prostaglandin production, thus eliminating the possibility that prostaglandin release is a consequence of uterine contraction. Since generation of prostaglandins can be initiated by mechanical stimuli such as touch or damage (Piper & Vane, 1971), the prostaglandin output from isolated uteri of pregnant rats could be a result of the stress of isolating the uterus, removing the contents and bathing it in an artificial salt solution.…”

Section: Discussionmentioning

confidence: 74%

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The contribution of prostaglandin production to contractions of the isolated uterus of the rat

Vane

Williams

1973

British J Pharmacology

190

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Summary1. Indomethacin and meclofenamate, both of which are potent inhibitors of prostaglandin synthetase, antagonized the contractor effects of oxytocin on the isolated uterus from the non-pregnant rat. Contractions induced by acetylcholine or prostaglandin F2a were not antagonized.2. Uteri from rats 17-22 days pregnant exhibited intermittent spontaneous contractions when used as isolated preparations. They also released prostaglandin-like activity (mainly similar to F2a) into the bathing fluid. Both the prostaglandin release and the uterine activity were abolished by indomethacin. Activity could be restored by addition of low concentrations of prostaglandin E2 or F2a.3. The release of prostaglandin F2a-like activity by the uteri increased dramatically on the expected day of delivery (day 22). 4. The results add force to the hypothesis that the spontaneous activity of some isolated organs is due to an intramural prostaglandin generation, and that increased uterine prostaglandin production contributes to the expulsion of the foetus.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 70%

Section: Introductionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 74%

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The contribution of prostaglandin production to contractions of the isolated uterus of the rat

Vane

Williams

1973

British J Pharmacology

190

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“…Rudzik & Miller, 1962;Levy & Tozzi, 1963;Tothill, 1967) have disputed the presence of excitatory ca-adrenoceptors within the normal oestrous cycle. There is now evidence that endogenous prostaglandins may be involved in motor responses of the uterus (Tothill, Rathbone & Willman, 1971;Aiken, 1972;Vane & Williams, 1973). This paper describes a study of the effect of temperature on the relative a-and B-adrenoceptor activities throughout the oestrous cycle.…”

mentioning

confidence: 99%

EFFECT OF TEMPERATURE ON CHANGES, INDUCED BY OESTRUS, in α‐ AND β‐ADRENOCEPTOR ACTIVITIES OF THE RAT UTERUS

Butterworth

Jarman

1974

British J Pharmacology

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The a-and 3-adrenoceptor activities of the isolated rat uterus during the oestrous cycle were intluenced greatly by temperature changes. During dioestrus, lowering the bath temperature to 250C from 400C increased two-fold the inhibition produced by (-)-adrenaline, (-)-noradrenaline, (-)-phenylephrine and (-)-isoprenaline. During oestrus adrenaline, noradrenaline and phenylephrine produced biphasic responses of contraction followed by inhibition at 40°C and isoprenaline produced only inhibition. At 250C the contractile a-responses either were abolished (phenylephrine) or greatly reduced (adrenaline and noradrenaline), while the inhibitory ,-effects of all four amines were increased.It has been generally accepted since the time of Ahlquist ( 1948) that the uterus of the rat contains f-adrenoceptors. However, Mann (1949) found that the uterus of the rat in oestrus contracted to noradrenaline and that there was a biphasic response to adrenaline. Butterworth & Randall (1970) showed that these effects are due to the presence of both at-and ,B-adrenoceptors throughout the oestrous cycle. Some workers (e.g. Rudzik & Miller, 1962;Levy & Tozzi, 1963;Tothill, 1967) have disputed the presence of excitatory ca-adrenoceptors within the normal oestrous cycle. There is now evidence that endogenous prostaglandins may be involved in motor responses of the uterus (Tothill, Rathbone & Willman, 1971;Aiken, 1972;Vane & Williams, 1973). This paper describes a study of the effect of temperature on the relative a-and B-adrenoceptor activities throughout the oestrous cycle.Methods Virgin, albino rats (Wistar strain), weighing 200-250 g, were used. The sexual state of the rat was determined by taking a vaginal smear immediately before killing by a blow to the head and bleeding out. The uterine horns were excised and 2-3 cm of the tissue from the ovarian end were set up in a 15 ml organ bath containing Tyrode solution aerated with 5% CO2 in 02. Uterine movements were recorded with an isotonic frontal writing lever (weight 0.5 g), moving on a smoked drum. Rats were used either in dioestrus or in oestrus, which was either natural or induced by oestradiol benzoate (0.5 mg s.c. given 3 days beforehand). After setting up the preparations, at least I h was allowed for the tissues to equilibrate before starting the experiment. The recordings were made at 400, 30°and 250 C. Thirty minutes were allowed to ensure that the uterus had settled down each time the bath temperature was altered. Doses were determined for each sympathomimetic amine which gave approximately 90% of a maximal contraction, or 50% inhibition of a near maximal response to acetylcholine. ResultsRats in dioestrus At the temperatures studied, all four amines produced solely inhibitory responses. At 40 C the mean inhibitory doses were phenylephrine (Phe) 12 ,g (range, 5 to 20 Mg, n = 5), noradrenaline (NA) 1.5 gg (0.75 to 2 ,g, n = 6), adrenaline (Ad) 18 ng (7 to 45 ng, n = 6) and isoprenaline (Iso) 4 ng (2 to 6 ng, n = 5). As the temperature was lowered, first to 30 C and then to 25...

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Effects of aspirin and acetaminophen in pregnancy and in the newborn

Rudolph¹

1981

Archives of Internal Medicine

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Inhibitors of prostaglandin synthesis are increasingly recommended for delaying premature delivery. However, such inhibitors--eg, aspirin, indomethacin, or naproxen--may interfere with uterine contractility, with maternal, fetal, and neonatal platelet function, and especially with fetal circulation and postnatal adaptation. The instillation of aspirin (50 to 90 mg/kg of fetal body weight) into the rumina of fetal lambs resulted in significant increase of pulmonary arterial pressure, which was directly related to constriction of the ductus arteriosus. Such pressure elevation may act as a stimulus to increased muscular development in the small vessels of the lung, which, in turn, could interfere with the rapid reduction in pulmonary vascular resistance normally occurring after birth. The effects of acetaminophen in pregnancy and in the newborn have not been studied extensively; when ingested in usual therapeutic doses, the available data have shown no adverse effects.

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Aspirin and Indomethacin Prolong Parturition in Rats: Evidence that Prostaglandins Contribute to Expulsion of Foetus

Cited by 190 publications

References 18 publications

The contribution of prostaglandin production to contractions of the isolated uterus of the rat

The contribution of prostaglandin production to contractions of the isolated uterus of the rat

EFFECT OF TEMPERATURE ON CHANGES, INDUCED BY OESTRUS, in α‐ AND β‐ADRENOCEPTOR ACTIVITIES OF THE RAT UTERUS

Effects of aspirin and acetaminophen in pregnancy and in the newborn

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