Effect of dietary restriction on triglyceride levels in the uterus isolated from pregnant rats. Influences of prostaglandins and indomethacin

Triglyceride (TGs) concentrations in uterine strips isolated from 14 or from 21 days-pregnant rats, either normal-fed or following a restricted-diet rats (50% food intake for 14 days), were measured. Determinations were made immediately after killing (0 min time or post-isolation) as well as after a period of incubation in glucose-free medium (60 min time or post-incubation). The post-isolation levels of TGs (0 min) in the uterus from normal-fed animals at 14 or at 21 days of pregnancy, were significantly higher in implantation sites than in the interembryonic segments. These values of TGs (0 time) did not change, in comparison to post-incubation concentrations (60 min), either without additions or in the presence of indomethacin (5 X 10(-6) M) or of prostaglandins (PGs) E1, E2 or F2 alpha (10(-7) M). At 0 time, uterine TGs of rats subjected to dietary restriction, increased as pregnancy progressed, more than in normal-fed controls. The post-incubation (60 min) pattern was different depending on the days of pregnancy; i.e. at 14 days, incubation in Krebs-Ringer Bicarbonate-medium (KRB) led to a significant fall unaffected by the addition of propranolol (10(-6) M). However, in the presence of indomethacin, TGs values had a level similar to the initial one (0 time). Furthermore, exogenous PGE1 or PGE2 failed to alter the effect of indomethacin, as PGF2 alpha did.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chronic underfeeding on uterine glycogen of rats. Influence of indomethacin and nordihydroguaiaretic acid

Glycogen values in uterine strips isolated from normal-fed estrous or diestrous rats, or from rats fed a restricted diet (50% of normal food intake for 25 days) were measured. Determinations were made immediately after killing (0 time or post-isolation) as well as after incubation in glucose-free medium (60 min time or post-incubation). The post-incubation levels of glycogen in the uteri from normal-fed animals diminished significantly in comparison to post-isolation values, and this decrement was not modified by the addition of indomethacin, nordihydroguaiaretic acid or exogenous prostaglandins E1, E2 or F2 alpha. In rats fed a restricted-diet, the initial glycogen values (0 time) were significantly lower than in normal-fed controls, but did not decline further after incubation in glucose-free medium (60 min time). The addition of indomethacin, acetylsalicylic acid or of nordihydroguaiaretic acid led to a significant fall in the glycogen levels, and exogenous PGE1, PGE2 or PGF2 alpha failed to alter the effects of the inhibitors. The values of PGE and PGF prostaglandins release to the medium by the uterus from restricted-diet rats did not differ from those obtained in the experiments with normal-fed animals. Administration of 17-beta estradiol to restricted-diet rats led to suppression of the effects of this diet on the glycogen concentration. The above results indicate that in rats subjected to a prolonged period of dietary restriction, the uterine glycogen becomes responsive to the effects of cyclooxygenase and lipoxygenase inhibitors, suggesting the operation of some regulatory mechanism during critical periods of nutrition.     

Thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin F2 alpha production by contracting pregnant rate uteri in vitro

While prostaglandin production by uterine tissue has been shown to be involved in the contractile mechanism of this tissue, less attention has focused upon the involvement of other prostanoids. We have simultaneously measured in vitro isometric contractility of pregnant rat uteri with the release of prostaglandin F2 alpha (PGF), 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) and thromboxane B2 (TXB2) into the bathing medium under various conditions. Frequency of uterine contractions and integrated contractile force (ICF) increased from 15 days of gestation and peaked at the time of parturition. Activity was generally greatest during the first 15 min of incubation except during parturition and on Day 1 postpartum when the uterine segment remained active for 1 h experimental period. Indomethacin (INDO) significantly reduced contractile activity regardless of gestational stage. PGF, TXB2, and 6-k-PGF1 alpha increased with gestational age, peaking at the time of parturition. Production was greatest during the first 15 min of incubation and INDO inhibited production of each prostanoid regardless of gestational stage. Imidazole (100 micrograms/ml) inhibited TXB2 production without affecting PGF or 6-k-PGF1 alpha levels. Frequency of contraction and ICF were not affected by imidazole treatment despite TXB2 reduction. These data demonstrate that the in vitro uterus from pregnant rats is capable of producing prostanoids other than prostaglandins and their production generally parallels uterine contractile activity. Thus, the possibility that these prostanoids are involved in physiologic changes during parturition warrants further investigation.     

Leukotrienes and myometrial activity of the term pregnant uterus

Biopsies from different segments of the pregnant human uterus were superfused in organ chambers and contractile activity was registered. Leukotriene C₄(LTC₄) caused inhibition of spontaneous but not noradrenaline induced contractile activity in strips from the cervix. This effect occured both in early pregnancy and at term. However, the lower and the upper uterine segment of the term pregnant uterus did not respond to LTC₄. The results represent a documentation of the segmental differentiation in the uterine response to eicosanoids.     

Leukotrienes and myometrial activity of the term pregnant uterus

Biopsies from different segments of the pregnant human uterus were superfused in organ chambers and contractile activity was registered. Leukotriene C4(LTC4) caused inhibition of spontaneous but not noradrenaline induced contractile activity in strips from the cervix. This effect occurred both in early pregnancy and at term. However, the lower and the upper uterine segment of the term pregnant uterus did not respond to LTC4. The results represent a documentation of the segmental differentiation in the uterine response to eicosanoids.     

Acute effects of a single ethanol injection on in vitro rat uterine spontaneous motility, on uteri prostaglandin production and on tissue metabolism of triglycerides.

The acute effects of ethanol (ETOH), injected at 3 g.kg-1i.p. on spontaneous contractions, on prostaglandin (PG) production and on the metabolism of triglycerides (TGs), have been studied in uterine strips obtained from rats at diestrus and suspended in glucose-containing or glucose-free solution. The absolute values of isometric developed tension (IDT: expressed in mg) recorded at 0 time (initial or post isolation determinations) and the frequency of contraction (FC), expressed as the number of contraction cycles during 20 min, were similar for uterine strips from controls and from ETOH treated rats. The uterine IDT and the FC expressed as percent changes from internal controls (0 time values) were explored during 180 min in uteri suspended in glucose medium. The magnitude of IDT decreased, as time progressed, both in controls as well as in ETOH-treated rats. Afterwards, uterine strips from controls exhibited a partial recovery of their contractile activity. This pattern of recovery was not observed in uterine strips from ETOH-treated rats. The uterine IDT, in the ETOH-injected animals after 180 min of activity, were significantly smaller than those of controls. On the other hand, the FC decreased progressively up to the end of the experimental period both in controls as well as in ETOH-treated rats. In glucose-free medium, the IDT of uterine strips from ETOH-injected animals diminished significantly more than controls from 100-180 min following isolation and mounting. In addition, the FC of uterine strips from the ETOH group of rats were significantly smaller than in controls suspended in glucose-free solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morinda lucida reduces contractility of isolated uterine smooth muscle of pregnant and non-pregnant mice.

The present work investigated the effect of Morinda lucida (M. lucida) extract on isolated uterine smooth muscle of pregnant and non-pregnant mice. Pregnant and non-pregnant mice were pretreated with oral stilboesterol (0.1 mg/kg body weight) and killed by cervical dislocation. Thin strips of the uterus were cut and mounted in a 20ml organ bath containing De Jalon solution bubbled with 95%O2-5% CO2 gas mixture. The strips were connected to a force transducer coupled to a Grass 7D Polygraph for the recording of isometric tension. Effects of graded concentrations of oxytocin (OXY; 10-5-10-2 mol/L), acetylcholine (ACh; 10-9-10-5 mol/L) and M. lucida extract (0.015-1.5 mg/ml) were recorded. Fresh uterine strips were then incubated with M. lucida extract for 5mins and cumulative response to OXY was repeated. Another set of fresh strips was incubated in L-NAME for 15mins and the cumulative responses to M.lucida extract were repeated. OXY resulted in increased contractile responses in both pregnant and non-pregnant uterine muscles. M. lucida resulted in relaxation of the uterine smooth muscle in both pregnant and non-pregnant mice at all doses. However, at 1.5mg/ml, M. lucida completely blocked spontaneous uterine contractions. Following incubation with L-NAME, M. lucida extract led to a slightly greater relaxation of the uterine strips. In conclusion, M. lucida reduced contractility of uterine smooth muscle in both pregnant and non-pregnant mice as well as blocking contractile responses to OXY and Ach in uterine smooth muscle of pregnant and non-pregnant mice. There was no significant alteration of M. lucida activity by L-NAME suggesting that the action of the compound on uterine muscle is not associated with impaired nitric oxide synthase.     

The effect of the antioxidant, butylated hydroxy anisole, on peroxide-induced and spontaneous activity of the uterus from the pregnant rat

Chorioamnionitis is associated with preterm labor. Leukocytes infiltrate infected tissue and secrete hydrogen peroxide (H2O2) and other reactive oxygen products as part of their bactericidal activity. We have therefore investigated the effect of H2O2 on activity of in vitro uteri from pregnant rats. Uteri from 18-day pregnant rats exposed to H2O2 showed a dose-dependent increase in both contractile activity and production of prostaglandins (PG) E2 and F2 alpha compared to untreated controls. The antioxidant butylated hydroxy anisole (BHA) inhibited the H2O2-induced uterine activity. Furthermore, BHA inhibited contractions and PG production from spontaneously contracting uteri from 21-day pregnant rats. H2O2 increased chemiluminescence of uterine tissue, an index of oxygen or lipid radical formation, whereas BHA inhibited this effect. The BHA inhibition of uterine activity was reversed by addition of PGE2 to the incubation chamber. These data support the hypothesis that reactive oxygen can regulate PG production by the uterus and suggests a role for reactive oxygen in infection-induced labor and perhaps normal term labor as well.     

The effect of aprotinin on luteolytic and uterine contractile mechanisms in the pregnant rat at term.

The effect of the kallikrein inhibitor aprotinin on luteal function, uterine activity and parturition was studied in primigravid pregnant rats. Luteal function was monitored by the determination of serum progesterone levels. Aprotinin given daily from Day 19 to Day 22 of gestation had no effect on progesterone concentrations compared to saline-treated controls, but indomethacin delayed the decline in progesterone levels over the same time period. Aprotinin treatment had no effect on fetal and placental weights from Days 19 to 22 of gestation. Aprotinin infusion in Day-22 pregnant rats resulted in a reduction in uterine motility (studied by continuous recording in conscious rats by means of an intrauterine microballoon) in 10/12 rats. Continuous infusion of aprotinin into rats which had been allowed to deliver one young resulted in a significantly prolonged duration of parturition compared to that in saline-infused controls. In one rat the delivery process was completely arrested and recommended only when the infusion was stopped. Aprotonin had no effect on either the spontaneous or oxytocin-induced uterine contractions of the isolated Day-22 pregnant rat uterus. It is concluded that the kallikrein-kinin system in the late pregnant rat does not appear to be involved in the luteolytic process but may play a functional role in the control of uterine and/or cervical function before and during parturition.     

Effect of chronic alcohol consumption on rat uterine spontaneous motility, prostaglandin production and triglyceride metabolism

The spontaneous isometric developed tension (IDT), the synthesis and release of prostaglandins (PGs) into the incubating medium and the metabolism of triglycerides (TGs) in uterine strips isolated from controls and chronic ethanol fed rats, were studied. In order to observe how the uterus of rats fed alcohol reacts during a situation of metabolic emergency, the above mentioned studies were done in the presence or in the absence of glucose in the incubating medium. The decrement of IDT as time progressed was significantly greater in strips obtained from rats which had been drinking 20% ETOH than in controls. Nevertheless, the absolute magnitude of the initial IDT was similar in both groups. On the other hand, the decline of the frequency of contractions (FC) of uterine strips isolated from controls and from ETOH-exposed rats, after 60 min of spontaneous activity was similar. When the uterine strips isolated from ETOH-exposed and from control rats were suspended in glucose-free solution they exhibited the same decrement of IDT and FC after 60 min of activity. The basal release of PGE1 and PGE2 was similar in control tissues incubated in medium containing glucose, but the output of PGE2 was significantly smaller than that of PGE1 in uterine strips isolated from ETOH-exposed rats. The production of PGE1 and PGE2 by uteri suspended in glucose-free medium was similar in control preparations. On the contrary the release of both PGs differs in uterine strips from ETOH-exposed rats, i.e. the output of PGE2 was significantly smaller than in controls and the release of PGE1 increased around 4-fold in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel enhancing effect of platelet activating factor (PAF) on glucose oxidation in uteri from pregnant rats. Participation of prostaglandins and leukotrienes

The effects of platelet activating factor (PAF) on glucose oxidation in uterine strips isolated from rats in the 4 th and 5 th day of pregnancy, were explored. PAF, at a concentration of 10(-10) and 10(-8) M, augmented significantly the generation of 14CO2 from labelled glucose in uteri from pregnant rats in the 4 th day of pregnancy. When the tissue was obtained from 5 days pregnant rats, the addition of PAF at 10(-8) increased significantly more than PAF at 10(-10) M the metabolism of glucose. On the other hand, PAF at 10(-8) M failed to alter the uterine basal production of 14CO2 from labelled glucose in animals at estrus. BN52021, a specific PAF antagonist employed at 10(-5) M, blocked completely the action of PAF in the pregnant rat uterus. PGE1, PGE2 and PGF2 alpha enhanced significantly the formation of 14CO2 from labelled glucose in uteri from 5 days pregnant rats. Indomethacin, a well known inhibitor of prostaglandin synthesis, did not alter the basal glucose metabolism in uteri from 5 days pregnant rats, but antagonized completely the stimulating action of PAF on 14CO2 production from labelled glucose an effect that was partially reverted by the addition of PGE1, PGE2 or PGF2 alpha (10(-7) M). Furthermore, nordihydroguaiaretic acid (NDHGA), a specific inhibitor of 5-lipoxygenase at 10(-5) M, as well as FPL-55712, an antagonist of leukotrienes (LTs), at the same concentration, blocked the action of PAF on the metabolism of glucose. The action of NDHGA was partially counteracted by the addition of LTC4 at 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is the spontaneous motility of isolated rat uterus controlled by prostaglandin E?

Variations in the spontaneous contractile activity during 6 hours following isolation of uterine horns from proestrus, metestrus and spayed rats, were explored. In estrus and metestrus preparations the contractions declined during 60 min and between 180–200 min a progressive spontaneous recovery (abolished by indomethacin) was observed up to 360 min. Uteri from proestrus and spayed animals exhibited a continuous depression without recovery during the whole experimental period. At 60 min, uterine horns from estrus animals (which showed a marked contractile decrement) released to the suspending medium significantly less prostaglandin E-like material than at 360 min, i.e. when contractions had almost completely recovered. No modification in the amount of prostaglandin F-like material was detected accompanying these spontaneous contractile variations. In the spayed group at 60 min of functioning (i.e. when the contractile impairment was significantly smaller than at a later time) the release of PGE was greater than at 360 min. These findings suggest a possible control of rat uterine contractions by PGE, rather than by PGF.     

Is the spontaneous motility of isolated rat uterus controlled by prostaglandin E?

Variations in the spontaneous contractile activity during 6 hours following isolation of uterine horns from proestrus, metestrus and spayed rats, were explored. In estrus and metestrus preparations the contractions declined during 60 min and between 180--200 min a progressive spontaneous recovery (abolished by indomethacin) was observed up to 360 min. Uteri from proestrus and spayed animals exhibited a continuous depression without recovery during the whole experimental period. At 60 min, uterine horns from estrus animals (which showed a marked contractile decrement) released to the suspending medium significantly less prostaglandin E-like material than at 360 min, i.e. when contractions had almost completely recovered. No modification in the amount of prostaglandin F-like material was detected accompanying these spontaneous contractile variations. In the spayed group at 60 min of functioning (i.e. when the contractile impairment was significantly smaller than at a later time) the release of PGE was greater than at 360 min. These findings suggest a possible control of rat uterine contractions by PGE, rather than by PGF.     

Effect of the long-term exposure of the isolated myometrium from nonpregnant rats to serum from pregnant women on its contractile activity and the beta-adrenergic reactivity

Pregnant women's blood serum (the whole as well as 50- and 100-diluted) did not alter parameters of spontaneous motility, i.e. it did not affect the uterus myocytes' spontaneous motility, whereas the whole or 50-diluted serum raised considerable the rat myometrium's beta-adrenoreaction. The data obtained suggest that the beta-adrenoreaction of the rat uterus' myocytes increases after a prolonged contact with pregnant women's blood serum which may be due to the beta-adrenoreceptor synthesis activation and to an increase in their concentration because of diffusion from the blood serum. This suggests existence of humoral mechanisms of the myometrium beta-adrenoreaction regulation, the mechanisms creating the optimum uterus' contractile activity.     

Inhibition of epoxy-eicosanoid degradation improves the tocolytic effects of indomethacin in the uterus from pregnant women

The incidence of preterm birth is an increasing problem. Indomethacin, a non-specific cyclooxygenase inhibitor, has been largely used as tocolytic in the treatment of preterm labor. The aim of the present study was to assess a putative synergistic tocolytic effect between the inhibition of the production of prostanoids and stabilization of epoxides fatty acids, particularly arachidonate on spontaneous uterine contractile activity. The experimental work was performed on uterine biopsies from consenting women undergoing elective cesarean delivery at term. Isometric tension measurements were performed on fresh human myometrial strips. Contractile activities have been monitored upon individual and combined treatments of indomethacin, DDMS, an inhibitor of hydroxy-eicosanoids production and AUDA, an inhibitor of epoxy-eicosanoids degradation. Interestingly, a significant and consistent synergic effect was observed when indomethacin and AUDA were simultaneously added, raising the possibility of a combined clinical use of cyclooxygenase and sEH inhibitors in attempt to treat preterm labor.     

Glucagon control of glycogenolysis in catfish tissues

1. In catfish (Ictalurus melas) after glucagon treatment blood glucose increased until 150 min, then it gradually decreased towards control values at the 5th hr. 2. In glucagon treated fish, liver glycogen levels were significantly lower then in controls 30 min after hormone administration; thereafter, liver glycogen levels returned rapidly to initial values. Glucagon did not induce any significant effect on the glycogen content in white and red muscles. 3. In liver slices, the addition of glucagon to the incubation medium significantly enhanced the glycogen phosphorylase activity and decreased the level of glycogen. Both phosphorylase activity and glycogen content of white and red muscle slices were practically unaffected by glucagon.     

Comparative utilization of glycerol and alanine as liver gluconeogenic substrates in the fed late pregnant rat

The appearance of plasma [14C]glucose in the inferior cava vein after a pulse of 0.2 mmol of [U-14C]L-alanine or [U-14C]glycerol/200 g body wt given through the portal vein was studied in fed 21 day pregnant rats and virgin controls under pentobarbital anesthesia. In both groups values were much higher when [U-14C]glycerol was the administered tracer than when [U-14C]L-alanine, and they were augmented in pregnant versus virgin animals at 1 min when receiving [U-14C]glycerol and at 2 min when receiving [U-14C]L-alanine. 20 min after the tracers rats receiving [U-14C]glycerol showed much higher liver [14C]glycogen and [14C]glyceride glycerol than those receiving [U-14C]L-alanine. Radioactivity present in liver as [14C]glyceride glycerol was greater in pregnant than in virgin rats receiving [U-14C]glycerol whereas radioactivity corresponding to [14C]fatty acids was lower in the former group receiving either tracer. At 20 min after maternal treatments fetuses showed lower plasma [14C]glycerol than [14C]alanine values but plasma [14C]glucose and liver [14C]glycogen values were much greater in fetuses from mothers receiving [U-14C]glycerol than [U-14C]L-amine. Besides showing the higher gluconeogenic efficiency in pregnant than in virgin rats, results indicate that at late gestation glycerol is used as a preferential substrate for both glucose and glyceride glycerol synthesis in liver.     

Gamma-linolenic acid improves the constancy of contractions in uteri from sprayed rats and is metabolized to prostaglandin E1 but not to bisenoic prostanoids

The effects of gamma-linolenic acid (GLA) on the time-dependent constancy of spontaneous contractions (isometric developed tension = IDT and frequency of contractions = FC) in uterine strips isolated from spayed rats, were explored. Moreover, the influence of the unsaturated fatty acid on the basal generation and release of tissue prostaglandins (PGs) as well as the conversion of labelled GLA into prostanoids by the uterine tissue and the effects of p-bromo-phenacyl-bromide (BPB), were also studied. GLA (10(-7)M), attenuated significantly the spontaneous decrement of contractile constancy exhibited by control preparations during a period of 180 min of activity in isolation, whereas BPB (10(5) M) resulted in an augmented and faster decrement of inotropic constancy. Spontaneous changes in the constancy of uterine motility as time progressed involved similarly both IDT and FC. After 180 min of activity in isolation a basal generation and release of PGs E and F of the series 1 and 2, were detected. The challenge with 10(-7) M GLA (delivered immediately after isolation) enhanced significantly the output of PGE1 but did not influence the generation and release of PGE2 or PGF2 alpha. BPB (10(-5) M) had no significant effect on the basal output of PGE1, PGE2 or PGF2 but completely prevented the enhancing action of GLA on the synthesis and release of PGE1. Labelled GLA was mainly converted to PGE1 by rat uterine segments and negligible counts in the 2-series of prostanoids, were observed. In presence of BPB (10(-5) M) the conversion of 1-14C-GLA, to PGE1 was almost completely abolished. The foregoing evidences suggest that exogenous GLA is metabolized by the spayed rat uterus via an elongase, forming di-homogamma-linolenic acid (DHLA), which in turn is substrate for cyclo-oxygenase peroxidase reactions yielding finally PGE1. No evidence of a delta 5-desaturase activity, converting DHLA into arachidonate and further derivatives, was detected. Coincidently, exogenous GLA was able to support a better contractile constancy as a function of time than that evidenced in untreated uterine strips isolated from castrated rats.     

In vivo exposure to carbon disulfide increases the contraction frequency of pregnant rat uteri through an indirect pathway

Exposure to CS2, an organic solvent, is associated with an increased rate of abnormal labor or dysmenorrhea. Contraction of quiescent uteri during pregnancy can cause preterm labor. We wish to know the effects of in vivo and in vitro exposures to CS2 on uterine contractions of mid-gestation rats. After 10-d exposure to 300 or 600 mg/kg CS2, uteri of pregnant rats were measured for contractile responses to various stimuli, such as KCl, oxytocin, carbachol or A23187, a calcium ionophore, using standard muscle bath apparatus. CS2 treatment significantly increased the contractile response to KCl, carbachol, and A23187. The increase to A23187 was the greatest. In contrast, in vitro exposure to CS2 immediately suppressed carbachol-induced contraction but did not affect spontaneous and KCl-induced contractions. Results showed the pregnant uterus of the rat is susceptible to CS2. The influence of in vivo exposure to CS2 on uterine contraction was opposite to that in vitro. The increased response of CS2-treated uteri to A23187 suggests that in vivo exposure to CS2 may sensitize contraction machinery to calcium through indirect pathways.     

Functional and histochemical characterization of a uterine adrenergic denervation process in pregnant rats

The time course of pregnancy-induced changes in the contractile responses of isolated uterine rings and sympathetic innervation pattern were studied using electric field stimulation and histofluorescence techniques, respectively, in intact and 6-hydroxydopamine-treated rats. Neurally mediated contractions elicited by field stimulation (0.6 msec, 1-70 Hz, 40 V) were measured in uterine preparations obtained from nonpregnant, 6-hydroxydopamine-treated and 5-, 10-, 15-, 18-, and 22-day (term) pregnant rats. At all frequencies, the amplitudes of contractions were highest in nonpregnant uteri. Stimulation at 1-2.5 Hz evoked contractions in 10-day pregnant uteri but failed to cause contractions on Day 5 and from Day 15 onward. In uterine preparations obtained from term and from 6-hydroxydopamine-treated rats, contractions could not be evoked by stimulation at 1-20 Hz. Fluorescence histochemistry of uterine adrenergic nerves revealed rich perivascular and myometrial innervation in nonpregnant and in pregnant rats through Day 10. Degeneration and loss of adrenergic nerve fibers was apparent by Day 15, and fluorescent myometrial and perivascular nerves were practically absent by Day 22. These findings demonstrate a progressive, frequency-related reduction of nerve-mediated uterine contractions beginning in midterm pregnancy, in parallel with a gradual loss of adrenergic nerve fibers. Pregnancy-induced nerve degeneration may promote the development of nonsynaptic alpha-adrenergic uterine contractile activity towards term. The reduced responsiveness of uterine smooth muscle to electric field stimulation in early pregnancy appears to be unrelated to alterations in uterine innervation but may be related to changes associated with implantation.