Field-stimulated strips of circular and longitudinal myometrium from virgin adult guinea-pigs were used to study the influence of ovarian steroids upon uterine responses to adrenaline and noradrenaline. Preparations were taken from animals (i) untreated, on day 9 or 10 of the oestrous cycle; (ii) treated for 14 days with oestradiol cypionate, beginning on day 9 or 10; and (iii) treated as in (ii) then given both oestradiol cypionate and progesterone for a further four days. Oestradiol treatment led to a 2-fold increase in the circulating level of progesterone; subsequent treatment of oestradiol-primed animals with progesterone resulted in even higher circulating progesterone levels, comparable with those occurring during mid-pregnancy in this species. Both adrenaline and noradrenaline produced phentolamine-sensitive motor responses of circular myometrial preparations from each treatment group. Steroid treatment was without significant effect on the potencies or maximal effects of the two amines on the circular muscle layer. Both catecholamines effected phentolamine-sensitive excitatory responses of longitudinal myometrial preparations from untreated guinea-pigs. Adrenaline usually produced propranolol-sensitive inhibitory responses of longitudinal preparations from oestradiol-treated animals, while noradrenaline did so only in a minority of cases. The potencies of adrenaline as an inhibitory agonist and noradrenaline as an excitatory agonist were markedly increased in preparations from oestradiol-primed animals.(ABSTRACT TRUNCATED AT 250 WORDS)
1This study describes the effects of ovarian steroid hormones upon the responses to adrenoceptor agonists of isolated myometrium, separated into its longitudinal and circular layers, and of costo-uterine muscle from guinea-pigs. The preparations were field-stimulated at 100s intervals, and the adrenoceptor agonists phenylephrine and isoprenaline produced enhancement or inhibition of the evoked contractions. 2 Isoprenaline produced propranolol-sensitive inhibitory effects in longitudinal and circular myometrium and costo-uterine muscle preparations from animals from all experimental groups: i.e. from nonsteroid-treated animals (ovariectomized and intact); intact animals treated with either oestrogen or progesterone alone; ovariectomized animals treated with oestrogen; ovariectomized and intact animals treated with progesterone following oestrogen priming; and from animals 1-4 days post-partum. Longitudinal myometrial preparations from progesterone-treated oestrogenprimed and from post-partum animals were most sensitive to this agonist. 3 Phenylephrine produced phentolamine-sensitive excitatory effects in circular myometrial and costo-uterine muscle preparations from animals from all the experimental groups. In contrast, propranolol-sensitive inhibitory responses to phenylephrine occurred in longitudinal myometrial preparations taken from animals treated with progesterone following oestrogen priming, and from post-partum animals. Longitudinal myometrium from animals from the remaining experimental groups exhibited phentolamine-sensitive excitatory responses to phenylephrine. 4 The basis for the selective effect upon the longitudinal myometrium of exposure to progesterone following a period of oestrogen priming, is discussed. The results described are consistent with the possibility that in the longitudinal layer of guinea-pig uterus exposed to progesterone following oestrogen priming there is an increase in the proportion of P-adrenoceptors in this layer. This increase may reduce the likelihood of contractions arising via direct stimulation of oa-adrenoceptors in this layer in response to sympathetic activation during pregnancy.
The influence of ovarian steroids upon responses to electrical stimulation and to activation of adrenoreceptors in field-stimulated preparations of longitudinal and circular myometrium from ovariectomised guinea-pigs has been investigated. Adult virgin guinea-pigs were bilaterally ovariectomised and were treated two weeks later with thrice-weekly injections of oestradiol cypionate for two weeks, or treated as in then given oestradiol cypionate and progesterone for a further four days. Control groups of bilaterally ovariectomised and sham ovariectomised animals remained untreated. Both myometrial layers from untreated ovariectomised guinea-pigs were atrophied. Responses to field stimulation in the circular myometrium were much smaller than those in the longitudinal layer. Steroid pretreatment, most notably treatment with oestradiol and progesterone, were associated with decreased and increased responsiveness to electrical stimulation in the circular and longitudinal myometrial layers respectively. Adrenaline and noradrenaline were consistently excitatory on preparations of circular myometrium from ovariectomised animals. Responses comprised either enhancement of electrically-evoked contractions, or, with the higher concentrations, the appearance of rapid contractions superimposed upon an increase in basal tone. The latter effects were also evident in preparations of circular myometrium from sham operated animals. In preparations of longitudinal myometrium from untreated ovariectomised animals noradrenaline consistently and adrenaline usually caused a simple enhancement of the magnitude of the evoked contractions. Phentolamine reduced the excitatory effects of both amines in both layers. In circular myometrium from the oestrogen-treated group both catecholamines produced phentolamine-sensitive enhancement of electrically-evoked contractions, but did not cause high frequency contractions or increased tonus. Noradrenaline and adrenaline produced qualitatively similar phentolamine-sensitive effects in preparations of longitudinal myometrium from this group.(ABSTRACT TRUNCATED AT 250 WORDS)
This paper describes some histological features of the costo-uterine muscle of the rat together with the effects of some sympathomimetic amines upon contractions evoked by field electrical stimulation of isolated preparations. Light and electron microscopy confirmed that the costo-uterine muscle of the rat consists of smooth muscle bundles, arranged longitudinally and interspersed with collagen. There were close contacts between individual cells within bundles. No axon profiles were observed. Histochemical techniques revealed only sparse catecholamine fluorescence at the border of the tissue in association with blood vessels. Isoprenaline, fenoterol, adrenaline, noradrenaline, salbutamol and phenylephrine consistently inhibited contractions evoked by field stimulation (40V, 30Hz, 2 ms for 5 sec every 200 sec). In contrast, tyramine was without effect upon electrically evoked contractions in concentrations of up to 200 mumol/l. The slopes of the log concentration-response curves of effective amines were similar, and all of these were capable of producing 100% inhibition of contraction. The potencies of the amines relative to isoprenaline = 100 were: fenoterol 135; salbutamol 16; adrenaline 16; noradrenaline 0.7; phenylephrine 0.1; tyramine less than 0.001. Propranolol, added to preparations in the absence of inhibitors of amine uptake and alpha-adrenoreceptors, competitively antagonised the effects of the amines. Schild plots had slopes which did not differ significantly from minus one, and the mean pA2 values fell within a narrow range, e.g. 8.65 with salbutamol; 9.20 with fenoterol. Mean pA2 values for propranolol with noradrenaline and isoprenaline were unaffected by the combined presence of phentolamine (10 mumol/l), cocaine (10 mumol/l), and corticosterone (10 mumol/l). The potencies of the agonists were also unaffected by the presence of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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