Specific drug responses of the uterine cervix in the
conscious ewe

Rafael Garcia Villar, P.L. Toutain, . Station de Pharmacologei-Toxicologie

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Rafael Garcia Villar, P.L. Toutain, . Station de Pharmacologei-Toxicologie. Specific drug responses of the uterine cervix in the conscious ewe. Colloques de l'INRA, 1982. hal-02782690

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SPECIFIC DRUG RESPONSES OF THE UTERINE CERVIX IN THE CONSCIOUS EWE

R. GARCIA-VILLAR, P.L. TOUTAIN

Station de Pharmacologie-Toxicologie I.N.R.A.,
180 chemin de Tournefeuille, 31300 Toulouse, France

The motility of the cervix of the ewe has not been studied because of the histological structure which revealed the presence of large amounts of collagen with only few smooth muscle cells embedded and therefore it has been described as an almost passive tissue (1). In addition, techniques currently used for the study of the motility of the uterus, e.g. direct observations through a laparotomy, indwelling pressure sensitive intraluminal catheters... are irrelevant for the cervix as well as the oviduct. Electromyography (EMG) already used to assess tubal motility in the conscious ewe (4) was successfully enlarged to the uterine cervix and supported by concomitant recording of mechanical activity as measured by strain gauge transducers (2). The motor activity profile of the cervix showed contractions of the cervical smooth muscle independent of the remainder of the uterus (3). This suggests that the cervix could exert a physiological role, more important than it was formerly supposed as well as the possibility of drug-induced motility changes. The aim of this report is to emphasize specific drug responses of the cervix vs. uterine horns.

METHODS

Electrodes made of Nichrome wires (0.12 mm diam., 200 cm in length) were implanted on the wall of the uterine cervix and horns of adult ewes of mixed breed, according to the technique earlier described. In addition, a strain gauge (Vishay type EA-06 125 BZ 350) pressed against a thin steel plate and inserted into a silastic(R) sheet (5 x 20 x 2 mm), was sewn close to one group of electrodes on the cervix and one of each uterine horn. Continuous monitoring of the electrical activity was obtained during a linear integrator circuit connected to a potentiometric recorder.
The effects of adrenaline chlorhydrate infusion (1.5µg/kg/min) were recorded on both horns and the cervix either alone or after administration of sympathetic antagonists: thymoxamine (Moxisylyte at the dosage of 1 mg/kg), yohimbine (0.1 mg/kg) or propranolol (0.1 mg/kg) administered intravenously as a single bolus injection in order to block α₁, α₂ and β adrenergic receptors respectively.

## RESULTS

**Patterns of activity.** - The activity patterns of the cervix of cycling, ovariectomized or pregnant ewes consisted of (i) single spikes or spike bursts of high amplitude (200 to 500 µV) and less than 0.5 sec in duration and thus termed short spikes (SS) or short spike bursts (SSB); (ii) spike bursts of low amplitude (20 to 60 µV) and a long duration (20 to 40 sec) thus termed long spike bursts (LSB) looking like oscillatory signals. The short spiking activity (SS and SSB), which constituted the main type of EMG events, occurred either sparsed (i.e. at a frequency lower than 4 spikes per min) and thus termed irregular spiking activity (ISA) or in a series at a frequency of 12-20 per min during 4 to 6 min, termed regular spiking activity (RSA).

On the integrated records, peaks of activity corresponding to each RSA were observed cyclically at hourly intervals, separated by periods of silence or lower activity corresponding to the ISA (fig. 1). These signals differed sharply from those of the uterine horns where strong bursts of spikes were recorded only during some active periods according to the sexual state.

Small variations in muscular tone of the cervix were recorded from the strain gauges during the isolated SSB. Strong and long-lasting changes occurred for each LSB. A progressive increase of the base-line with superimposed small contractions was registered during the phases in which SSB occurred in

**Drug-induced responses.** - The responses of both cervix and uterine horns to adrenaline infusion either alone or after single bolus administration of receptors specific antagonists as shown in figure 2 consisted of an increased frequency of the cervical short spike bursts and a continuous activity of low amplitude on the uterus. After thymoxamine, adrenaline infusion was followed by a similar rise in cervical spiking activity while a low level activity was recorded on the uterine horns. In contrast, yohimbine (0.1 mg/kg, IV) prevented the cervical activation by adrenaline infusion, while the uterine horns were scarcely affected. After propranolol (0.1 mg/kg) adrenaline infusion elicited a marked stimulation of both horns and cervix.

A few minutes after the end of each adrenaline infusion, the uterine horns displayed a strong activity phase of about 10 min duration, except after
<figure><img src="image_2.png" /><figcaption>Fig. 1 - Integrated recording of the uterus and the cervix in the ewe at the onset of oestrus.</figcaption></figure>

<figure><img src="image_3.png" /><figcaption>Fig. 2 - Effects of adrenaline infusion on the electrical spiking activity summed at 20-sec intervals of both horn and cervix in the ewe at the onset of oestrus. The infusion of adrenaline is preceded by the injection (Δ) of moxisylate (mox), yohimbine (yoh) and propranolol (prop) at 0.1 mg/kg.</figcaption></figure>
the β blocker propranolol. Such late responses were never observed on the cervix, thus suggesting that the pathways implicated either in activation or inhibition of both parts of the female genital tract, were different.

## DISCUSSION

The technique used for this study offers several advantages over other current techniques. Thin wire electrodes directly implanted into the wall and strain gauges sewn on the serosa do not distort the cervical canal nor interfere with its spontaneous motility for months, a period of time often necessary for reproduction studies. A striking feature revealed by both electrical and mechanical recordings is the existence of a cyclic pattern of cervical activity termed here regular spiking activity. This pattern has been recorded on cycling, ovariectomized and pregnant ewes, independently of the uterus (3). The recurrence of this pattern varied according to the sexual status and the pattern could be mimicked by an infusion of adrenaline.

The evaluation of drug action on the motility of the female genital tract, i.e. short term and long term effects of a drug could be assessed only following the occurrence of these cyclic motor events. From these results it is concluded that enhancement of the motility of the genital tract is related to adrenergic receptors via α₁ receptors for the uterus and α₂ for the cervix.

## References

(1) Fitzpatrick, R.J. - The activity of the uterine cervix in ruminants. Vet. Rec., 1957, **43**, 713-717.

(2) Garcia-Villar, R., Toutain, P.L., Ruckebusch, Y. - Electromyographic evaluation of the spontaneous and drug-induced motility of the cervix. J. Pharmacol. Meth., 1982, **7**, 83-90.

(3) Garcia-Villar, R., Toutain, P.L., More, J., Ruckebusch, Y. - Spontaneous motility of the cervix in cycling and ovariectomized ewes and changes induced by exogenous hormones. J. Reprod. Fert.,

(4) Ruckebusch, Y., Buéno, L. - An electromyographic study of the uterotubal activity in the ewe. J. Reprod. Fert., 1976, **47**, 221-227.

## Résumé

Etude électromyographique de l'activité cervico-utérine chez la brebis non gestante et de sa réponse à la stimulation adrénergique. La perfusion intraveineuse lente de divers agonistes et antagonistes de type α et δ est en faveur de l'existence d'une action excito-motrice par l'intermédiaire de récepteurs α₁ pour l'utérus et α₂ pour le cervix.
SECOND CONGRESS OF THE
EUROPEAN ASSOCIATION FOR
VETERINARY PHARMACOLOGY
AND TOXICOLOGY

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Pharmacologie et
Toxicologie vétérinaires

2e Congrès européen

Toulouse (France), 13-17 septembre 1982

inra

INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

149, rue de Grenelle - 75341 Paris Cedex 07