Summary. Guinea-pigs were anaesthetized at three stages of pregnancy. Intrauterine pressure was recorded for a 1-h control period and during 10-min intravenous infusions of noradrenaline at rates of 1·0 and 10 μg/(min·kg). The mean and maximum amplitude of contractions occurring during the infusions was compared with that of contraction cycles registered in the control period. At 18–21 and 35–43 days post coitum, noradrenaline invariably evoked a rapid and sustained rise in intrauterine pressure, the amplitude of the contractions being greater than during spontaneous contraction cycles recorded in the control period. In late pregnancy, 59–68 days p.c., infusion of 1·0 μg noradrenaline/(min·kg) failed to elicit a clear response; contractions occurring during infusion of 10 μg noradrenaline/(min·kg) had amplitudes similar to those of the control period and were without a sustained contracture. The absence of denervation hypersensitivity, despite the occurrence of sympathetic denervation in the course of pregnancy, may be due to a generalized effect on excitation—contraction coupling, possibly caused by relaxin.
A. M. CARTER and T. OLIN
Responses of the myometrial and maternal placental circulations to adrenergic stimulation and blockade have been studied in the rabbit by serial angiography after selective catheterization of the urogenital artery. Changes in myometrial activity and arterial blood pressure have been registered and taken into account. Myometrial and placental blood flow was reduced by a few nanograms of noradrenaline or adrenaline, but increased after blockade of αadrenoceptors with phenoxybenzamine or thymoxamine. The main effect of phentolamine was to evoke a long series of myometrial contractions, which counteracted the tendency of this drug to improve placental perfusion. The β-blocking agent, propranolol, had no effect at all on the parameters studied. Isoprenaline did not clearly affect myometrial and placental blood flow. Isoxsuprine, however, caused a slight increase by dilating the uterine arteries, possibly due to its papaverine-like properties. Both isoprenaline and isoxsuprine tended to depress myometrial activity. None of the drugs tested markedly affected distribution of uterine blood flow between the uterine wall and the placentae.
Lena Mårtensson and A. M. Carter
Summary. Noradrenaline infusions were given to anaesthetized guinea-pigs in early (19–23 days) and near-term (61–66 days) pregnancy. Radioactive microspheres (15 μm) were used to determine blood flow in various regions of the genital tract. In late gestation, a 10-min intravenous infusion of 1 μg noradrenaline/min/kg elicited moderate increases in vascular resistance that were counteracted by the pressor response. Uterine and placental blood flow remained unchanged, although there was a 27% decrease in perfusion of the uterine cervix and a fall of 19% in vaginal blood flow. In early pregnant guinea-pigs, blood pressure rose but vascular resistance was unaffected, resulting in an augmentation of placental blood flow. During infusion of 10 μg noradrenaline/min/kg, the vasoconstrictor response in late pregnancy was accentuated, and a strong decrease in tissue perfusion was noted in the placenta (—36%), uterine horns (—39%), cervix (—70%) and vagina (—56%). At the higher rate of noradrenaline infusion, vascular resistance also increased in the genital tract of early pregnant animals, although to a lesser extent than in late pregnancy. The results indicate an enhancement of the vasoconstrictor response to circulating catecholamines in near-term pregnancy.
N. EGUND and A. M. CARTER
The distribution of arteries and veins to the uterine and maternal placental vascular beds of the guinea-pig was studied in vivo by serial angiography and post mortem by the injection of barium sulphate suspension. The main features of the fetal placental vessels were also demonstrated. There is a dual arterial supply to each uterine horn, the uterine and ovarian arteries joining to form a continuous loop. The radial arteries which arise from the arterial loop and supply the placentae pursue a meandering course and are widely dilated. The haemodynamic implication of this configuration is that the placentae are evenly perfused with blood at a low flow velocity and a relatively low mean pressure. The veins draining the uterus are of wide calibre, presenting little resistance to flow and allowing for a small pressure gradient between the placentae and the vena cava. Veins leaving the lateral part of the uterine horn pass through the network of arteries supplying the ovary, but no special arrangement for countercurrent exchange could be demonstrated. Techniques are described for the selective catheterization of the uterine and ovarian arteries and for super-selective catheterization of the utero-ovarian veins from a jugular vein.
A. M. CARTER and T. OLIN
The effect of acetylcholine upon uteroplacental blood flow was studied by X-ray angiography following selective catheterization of the urogenital artery of the rabbit. Injection of acetylcholine into the artery usually increased the total uterine blood flow. In some cases, this entailed an increase in maternal placental blood flow but, in others, the blood supply to the placenta was cut off and the increased flow passed through the superficial myometrial vessels and, possibly, arteriovenous short circuits. The dichotomy in vascular response depended upon a variation in the myometrial response. In some animals, acetylcholine evoked a large contraction, which curtailed placental flow by compressing blood vessels. In others, the myometrium reacted slightly or not at all to acetylcholine and placental blood flow was able to increase. The vascular and myometrial responses to acetylcholine could be inhibited by previous administration of atropine or butylscopolamine.
A. M. CARTER, J. GÖTHLIN and T. OLIN
The uterine and maternal placental vasculature of the rabbit has been studied by serial angiography after selective catheterization of the urogenital artery or the corresponding vein and in specimens injected with barium sulphate suspension and gelatin. The uterus is supplied with blood through long, spiral arteries. Some of these perfuse the myometrium whilst others enter the placentae, opening into large arterial sinuses which supply the labyrinth through wide efferent vessels. It is suggested that blood pressure is reduced and pulse pressure damped during passage of the blood through the spiral arteries and that the function of the sinuses is to raise the lateral pressure and reduce the linear velocity, so that a slow even perfusion of the placental labyrinth can be achieved. Cross connections between the spiral arteries and a plexus of finer arterial vessels beneath each placenta enable redistribution of blood flow between the myometrium and placentae. In addition, there are probably arteriovenous anastomoses in pregnant as well as non-pregnant uteri. A sphincter mechanism in the placental feeding arteries is postulated to prevent intrapartum haemorrhage after delivery of the placentae and possibly to regulate maternal placental blood flow during pregnancy. Total uterine blood flow was estimated to be about 30 ml/min. Circulation time through the myometrium was much less than that through the placenta.
D. A. Carter, J. M. Pennington and S. A. Whitehead
Summary. Domperidone at a dose of 4 mg/kg significantly raised circulating prolactin levels in male and female rats although this increase was approximately 4-fold higher in females compared with males. No effect on LH secretion was observed. The LH and prolactin responses to Gn-RH and TRH respectively were investigated with isolated perfused pituitary glands obtained from domperidone-pretreated animals. For females, the basal release of prolactin was raised by domperidone pretreatment and the responsiveness of the pituitary to Gn-RH was markedly attenuated. When domperidone was added to the perfusing media, high concentrations (100 μg/ml) reduced both the basal and TRH-stimulated prolactin secretion from pituitaries of untreated male and female rats although lower doses (1 μg/ml and 10 ng/ml) were ineffective in altering prolactin release. The pituitary LH responses to Gn-RH were similarly reduced by the presence of 100 μg domperidone/ml in the medium.
P.-O. B. Sjöquist, L. Bjellin and A. M. Carter
Summary. Ovarian, uterine and vaginal blood flow were determined in 22 virgin guinea-pigs by the tracer microsphere technique. Measurements were made during oestrus, when cornified cells appeared in the vaginal smear (Day 1), or during the luteal phase of the cycle (Day 11). The total rate of blood flow to the genital tract was 0·58 ml. min−1 on Day 11 and 2·92 ml. min−1 on Day 1. This difference was largely due to an 8-fold increase in uterine blood flow from 0·26 to 2·01 ml. min−1. Although uterine weight increased over the same period, there was a significant increase in uterine tissue perfusion from 0·32 to 1·18 ml.min−1.g−1. The vagina exhibited a similar pattern, including a significant increase in tissue perfusion. Ovarian blood flow decreased from a value of 0·19 ml.min−1 during the luteal phase to 0·10 ml.min−1 at oestrus. Perfusion of the ovarian tissue was considerably greater on Day 11 than on Day 1 (2·86 versus 1·39 ml.min−1.g−1).
L. Bjellin, P.-O. B. Sjöquist, L. Mårtensson and A. M. Carter
Summary. Two sizes of microsphere were used to determine regional blood flow in pregnant guinea-pigs. Tissue perfusion measured with 50 μm microspheres was significantly greater than that measured with 15 μm microspheres in the small intestine, uterus, vagina, and placenta. A significantly larger proportion of the smaller microspheres passed through the systemic vasculature and could be detected in the lungs.
Q. Zeng, N-C. Foo, J. M. Funkhouser, D. A. Carter and D. Murphy
The rat vasopressin gene contains two transcriptional promoters; the activity of one is confined to the hypothalamus, while the other is testis specific. To define the sequences mediating the cell-specific expression of the vasopressin gene, we introduced rat vasopressin transgenes into the rat germ line. Neither transgene 1.5-Vβgal-0.2, which consists of the entire vasopressin structural gene containing a 3 kbp β-galactosidase reporter element in exon III, flanked by 1.5 kbp upstream of the start of hypothalamic transcription and 0.2 kbp downstream of the polyadenylation site, nor transgene 3-Vβgal-0.2, which consists of the entire VP structural gene containing a 3 kbp β-galactosidase reporter element in exon III, flanked by 3 kbp upstream of the start of hypothalamic transcription and 0.2 kbp downstream of the polyadenylation site, were expressed in the hypothalamus. This contrasts with a previously described transgene consisting of the rat vasopressin structural gene containing a reporter in exon III, flanked by 5 kbp of upstream and 3 kbp of downstream sequences, which is expressed in vasopressinergic hypothalamic neurones. Both the 3-Vβgal-0.2 and 1.5-Vβgal-0.2 transgenes were expressed in testicular germ cells using a promoter located within the α-galactosidase reporter element. Transgene RNA was most abundant during the late stages of meiosis. Rats bearing vasopressin-β-galactosidase transgenes provide new models for the study of the mechanisms whereby an epigenetic choice is made between the use of a germ cell or a somatic promoter, and the stage-specific transcriptional regulation of a germ cell promoter during spermatogenesis.