Insulin release from the pancreas and fuel metabolism during late gestation in chemically diabetic rats

The effects of chemical diabetes and fasting on fuel metabolism and insulin secretory activity in late pregnancy were investigated. Female Wistar rats were made chemically diabetic (CD) by intravenous injection of streptozotocine (30 mg/kg) 2 weeks before conception. When CD pregnant rats were fed, plasma glucose and insulin levels were not significantly different from those of normal pregnant rats. Ketone body levels, however, were higher in CD pregnant rats than in normal pregnant rats, indicating insulin resistance in CD rats. Insulin secretion from the perfused pancreas caused by arginine or glucose was markedly decreased in CD pregnant rats. The pregnant rats were fasted for 2 days, from day 19 to 21 of gestation. Plasma glucose and insulin concentrations decreased similarly in the two groups, whereas ketone body concentrations in CD pregnant rats were significantly higher than those in normal pregnant rats. Glucose-induced insulin secretion by the perfused pancreas was markedly attenuated by fasting and was not significantly different in normal and CD pregnant rats. These observations suggest that diabetes mellitus accelerates starvation in late gestation, due to increased insulin resistance and poor insulin secretion, and that fasting in diabetic pregnancy amplifies ketogenesis.     

Pregnancy alters cardiac receptor afferent discharge in rats

Reflex effects of cardiac receptor (CR) stimulation are attenuated in pregnant rats. We tested whether CR afferent discharge is reduced during pregnancy by measuring single fiber activity in response to increases in right atrial pressure (RAP) in anesthetized pregnant and virgin rats with sinoaortic denervation. Single fiber activity was isolated from fine filaments of the right cervical vagus nerve. Changes in CR discharge, RAP, and arterial pressure were recorded in response to atrial saline injections (25-300 microl). Resting RAP was similar between groups, and spontaneous CR discharge was similar in pregnant rats (1.95+/-0.21 Hz) and in low-frequency (LF) receptors in virgin rats (1.30+/-0.2 Hz). In virgin, but not pregnant rats, a subset (24%) of CR had higher-frequency (HF) spontaneous discharge (9.91+/-1.19 Hz). During stimulation, the level of RAP above which CR firing increased was significantly higher in pregnant rats, but CR activity was clustered into an LF discharge range. Thus gestation appears to reduce the activity of CR afferents, possibly by increasing stimulus threshold or by selective inactivation of a subset of HF discharging receptors.     

Epithelial and adipose cells isolated from mammary glands of pregnant and lactating rats differ in 11 beta-hydroxysteroid dehydrogenase activity

Both adipose and epithelial cells isolated from the mammary glands of pregnant and lactating rats show 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity, as measured by conversion of corticosterone to 11-dehydrocorticosterone. Activity in adipose cells from pregnant rats is 3-fold higher than in lactating rats. Epithelial cells from pregnant rats show one-twentieth of the activity of adipose cells, and activity is lower still in epithelial cells from lactating rats. Explants incubated for 48 h extensively metabolized corticosterone to 11-dehydrocorticosterone, and to a much lesser extent to a second unknown metabolite which is found in tissue extracts but not conditioned medium. Mammary gland 11-HSD may thus constitute one of the physiological mechanisms preventing premature milk production in response to glucocorticoids.     

Pregnancy-associated reduction in vascular protein kinase C activity rebounds during inhibition of NO synthesis

Vascular reactivity has been shown to be reduced during pregnancy and to be enhanced during chronic inhibition of nitric oxide (NO) synthesis in pregnant rats; however, the cellular mechanisms involved are unclear. The purpose of this study was to investigate whether the pregnancy-induced changes in vascular reactivity are associated with changes in the amount and/or activity of vascular protein kinase C (PKC). Active stress as well as the amount and activity of PKC was measured in deendothelialized thoracic aortic strips from virgin and pregnant rats untreated or treated with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). In virgin rats, the PKC activator phorbol 12,13-dibutyrate (PDBu, 10(-6) M) and the alpha-adrenergic agonist phenylephrine (Phe, 10(-5) M) caused significant increases in active stress and PKC activity that were inhibited by the PKC inhibitors staurosporine and calphostin C. Western blot analysis in aortic strips of virgin rats showed significant amount of the alpha-PKC isoform. Both PDBu and Phe caused significant translocation of alpha-PKC from the cytosolic to the particulate fraction. Compared with virgin rats, the PDBu- and Phe-stimulated active stress and PKC activity as well as the amount and the PDBu- and Phe-induced translocation of alpha-PKC were significantly reduced in late pregnant rats but significantly enhanced in pregnant rats treated with L-NAME. The PDBu- and Phe-induced changes in active stress and the amount, distribution, and activity of alpha-PKC in virgin rats treated with L-NAME were not significantly different from that in virgin rats, whereas the changes in pregnant rats treated with L-NAME + the NO synthase substrate L-arginine were not significantly different from that in pregnant rats. These results provide evidence that a PKC-mediated contractile pathway in vascular smooth muscle is reduced during pregnancy and significantly enhanced during chronic inhibition of NO synthesis. The results suggest that one possible mechanism of the pregnancy-associated changes in vascular reactivity may involve changes in the amount and activity of the alpha-PKC isoform.     

Preservation of the effects of pregnancy on rat islets of Langerhans in tissue culture.

Islets of Langerhans, isolated from normal or 19-day pregnant rats, were cultured for 20 h at 37 degrees C in tissue culture medium 199. When islets were cultured in medium containing low glucose (5.5 mM), the higher adenylate cyclase activity and insulin secretory responses characteristic of islets from pregnant rats were maintained during the test period of 29 h. Islets from normal and pregnant rats were also cultured for 20 h in medium containing a very high glucose concentration (83.3 mM) in order to load the B cells with glycogen. It was found, after glycogen loading, that, while adenylate cyclase activity increased to a greater extent in islets from pregnant rats than controls, this activity was not increased in proportion to the striking changes in insulin release rate observed in pregnant rat islets. The results show that the difference in insulin secretory response between islets from normal and pregnant rats may be preserved when the islets are cultured for 20 h, and that these differences are enhanced for a variety of reasons after culture of islets in 83.3 mM glucose.     

Regulation of insulin release from isolated islets of Langerhans of the rat in pregnancy. The role of adenosine 3':5'-cyclic monophosphate

1. The concentrations of cyclic AMP were compared in islets of Langerhans isolated from the pancreases of normal female and pregnant rats and were higher in islets in pregnancy. 2. There was also a significant increase in adenylate cyclase activity in homogenates of islets from pregnant rats compared with those from normal rats. 3. Increased cyclic AMP concentration in islets from pregnant rats was reflected in increased protein kinase activity. When the cyclic AMP-dependent protein kinase activity was increased by 3-isobutyl-1-methylxanthine this stimulated activity was significantly greater in pregnancy. 4. Insulin-secretion studies with islets from normal and pregnant rats showed that theophylline or 3-isobutyl-1-methylxanthine, which raise intracellular cyclic AMP concentrations, caused a significantly greater insulin secretion in pregnancy. 5. It was also found that in the presence of a glucose concentration too low to stimulate insulin secretion, the latter could be induced if the cyclic AMP concentrations were raised sufficiently with 3-isobutyl-1-methylxanthine. 6. It is suggested that the higher cyclic AMP concentrations observed in islets in pregnancy mediate the greater insulin-secretory capacity, as well as the greater sensitivity of these islets to low glucose concentrations.     

High-sodium intake prevents pregnancy-induced decrease of blood pressure in the rat

Despite an increase of circulatory volume and of renin-angiotensin-aldosterone system (RAAS) activity, pregnancy is paradoxically accompanied by a decrease in blood pressure. We have reported that the decrease in blood pressure was maintained in pregnant rats despite overactivation of RAAS following reduction in sodium intake. The purpose of this study was to evaluate the impact of the opposite condition, e.g., decreased activation of RAAS during pregnancy in the rat. To do so, 0.9% or 1.8% NaCl in drinking water was given to nonpregnant and pregnant Sprague-Dawley rats for 7 days (last week of gestation). Increased sodium intakes (between 10- and 20-fold) produced reduction of plasma renin activity and aldosterone in both nonpregnant and pregnant rats. Systolic blood pressure was not affected in nonpregnant rats. However, in pregnant rats, 0.9% sodium supplement prevented the decreased blood pressure. Moreover, an increase of systolic blood pressure was obtained in pregnant rats receiving 1.8% NaCl. The 0.9% sodium supplement did not affect plasma and fetal parameters. However, 1.8% NaCl supplement has larger effects during gestation as shown by increased plasma sodium concentration, hematocrit level, negative water balance, proteinuria, and intrauterine growth restriction. With both sodium supplements, decreased AT1 mRNA levels in the kidney and in the placenta were observed. Our results showed that a high-sodium intake prevents the pregnancy-induced decrease of blood pressure in rats. Nonpregnant rats were able to maintain homeostasis but not the pregnant ones in response to sodium load. Furthermore, pregnant rats on a high-sodium intake (1.8% NaCl) showed some physiological responses that resemble manifestations observed in preeclampsia.     

Matrix metalloproteinase-2 activity, protein, mRNA, and tissue inhibitors in small arteries from pregnant and relaxin-treated nonpregnant rats.

Vascular gelatinase activity is essential for pregnancy- and relaxin (Rlx)-induced renal vasodilation and hyperfiltration in rats. The objective of this study was to further elucidate the mechanisms for the increase in vascular matrix metalloproteinase (MMP)-2 activity caused by pregnancy and Rlx. We first corroborated our earlier work by showing that pro- and active forms of MMP-2 were increased in small renal arteries from pregnant compared with virgin rats and Rlx-treated compared with vehicle-treated nonpregnant rats. We next investigated other artery types and showed that MMP-2 activity was upregulated in mesenteric arteries from pregnant rats (pro-MMP-2 by 50% and active MMP-2 by 40%, both P<0.05) and from Rlx-treated nonpregnant rats (pro-MMP-2 by 50% and active MMP-2 by 90%, both P<0.005) compared with their respective controls. To corroborate these results obtained by gelatin zymography, pro-MMP-2 protein was determined by Western analysis in the same small arteries. Pro-MMP-2 protein was increased in small renal arteries from pregnant compared with virgin rats and from Rlx- compared with vehicle-treated nonpregnant rats: pro-MMP-2-to-beta-actin ratio=0.29 vs. 0.21 (P<0.01) and 0.43 vs. 0.32 (P<0.005). Findings were similar for mesenteric arteries. MMP-2 mRNA as measured by real-time PCR was increased in small renal arteries from pregnant and Rlx-treated nonpregnant rats compared with their respective controls. There were no significant differences in tissue inhibitor of metalloproteinase (TIMP-1 or TIMP-2) activity by reverse zymography in small renal arteries. Thus increases in MMP-2 mRNA and protein expression are major factors contributing to increased MMP-2 activity in small arteries from pregnant and Rlx-treated nonpregnant rats.     

Streptozotocin-Induced Diabetes Decreases Mammary Gland Lipoprotein Lipase Activity and Messenger Ribonucleic Acid in Pregnant and Nonpregnant Rats

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity in adipose tissue and development of hypertriglyceridemia. To determine how a condition of severe insulin deficiency affects mammary gland LPL activity and mRNA expression during late pregnancy, streptozotocin (STZ) treated (40 mg/kg) and non-treated (control) virgin and 20 day pregnant rats were studied. In control rats, both LPL activity and mRNA were higher in pregnant than in virgin rats. When compared to control rats, STZ-treated rats, either pregnant or virgin, showed decreased LPL activity and mRNA content. Furthermore, mammary gland LPL activity was linearly correlated with mRNA content, and either variable was linearly correlated with plasma insulin levels. Thus, insulin deficiency impairs the expression of LPL in mammary glands, revealing the role of insulin as a modulator of the enzyme at the mRNA expression level.     

Uterine estrogen sulfatase activity at the time of blastocyst implantation in the rat

The conversion of estrone sulfate (E1S) to estrone (E1) was measured during the in vitro incubation of the labeled sulfoconjugate with implantation sites (IS) and nonimplanted regions (NIS) of uterine horns from 6-day pregnant rats. Extensive metabolism of E1S occurred in both tissues, being noticeably less (29.31%) in IS than in NIS. Estrogen sulfatase activity present in the uterus of ovariectomized virgin rats was found to be higher than in both uterine regions of the pregnant rats. We suggest that E1S present in uterine fluids may be accessible to be metabolized into unconjugated estrogens by both intrauterine tissues of 6-day pregnant rats. This metabolism could be locally modulated in IS through the participation of the estrogen sulfatase, the activity of which is in turn controlled by the presence of free estrogens, possibly synthesized and/or secreted by the embryo, which has been shown to inhibit the sulfohydrolase activity.     

Estrogen effects on platelet-activating factor and platelet-activating factor acetylhydrolase activity in rat uterus during the late stages of pregnancy.

The platelet-activating factor (PAF) concentration of the uterus spontaneously increased during pregnancy. When 17alpha-ethynylestradiol (0.25 mg/kg) was administered subcutaneously to pregnant rats for 3 days starting on Day 17 of pregnancy, some rats delivered prematurely on Day 20. However, none of the vehicle-treated (80% dimethylsulfoxide and 20% ethanol) pregnant rats delivered prematurely. The PAF concentration of the uterus in pregnant rats treated with 17alpha-ethynylestradiol was significantly higher than in those treated with vehicle on Days 19 and 20. On the other hand, the specific activity of uterine PAF-acetylhydrolase (PAF-AH) in pregnant rats treated with 17alpha-ethynylestradiol was significantly lower than in those treated with vehicle on Days 19 and 20, and the plasma PAF-AH activity in pregnant rats treated with estrogen was also significantly lower than in treated with vehicle on Days 18, 19, and 20. These findings indicate that estrogen increases PAF concentrations in the rat uterus, and this was correlated with a decrease in PAF-AH in the uterus and plasma. The increase in PAF concentrations in the uterus may be related to premature delivery and labor caused by PAF's known effect on myometrial contraction.     

Metabotropic glutamate receptor/phospholipase C pathway is increased in rat brain at the end of pregnancy

Wistar pregnant rats were sacrificed at the end of pregnancy and the status of metabotropic glutamate receptors/phospholipase C (mGluR/PLC) pathway was studied in brain from pregnant and non-pregnant female rats. Pregnancy causes a significant increase in metabotropic glutamate receptors number, determined by radioligand binding assay, without significant changes on receptor affinity. Similar increase in mGluR(1) type was obtained by immunoblotting assay using specific anti-mGluR(1) antibody. However, no significant differences were observed in mGluR(5) type, suggesting that the increase detected by radioligand assays could be due to mGluR(1) up-regulation. On the other hand, a significant increase in the alpha subunit of G(q) protein was also detected in pregnant rats by immunoblotting assays. Real-time PCR experiments revealed a significant increase in gene expression of metabotropic glutamate receptors and G(q) proteins. Neither protein level nor gene expression of phospholipase C beta(1) isoform was altered in pregnant rats. However, an increase in basal and agonist-stimulated phospholipase C activity was observed in membranes from pregnant rats. These results suggest that gestational period causes the up-regulation of both metabotropic glutamate receptors and coupled G(q)-protein and, in turn, an increase in phospholipase C activity.     

Regulation of 6-phosphofructo-1-kinase from the epithelial cells of rat small intestine during pregnancy and lactation

The regulation of 6-phosphofructo-1-kinase (PFK) in the epithelial cells of rat small intestine was studied during pregnancy and lactation. The total activities and activity ratios (activity at 0.5 mM fructose 6-phosphate at pH 7.0/activity at pH 8.0 (nu 0.5/V] of the partially purified mucosal PFK were found to increase initially in early pregnant rats (11-12 days of gestation) and to fall back to normal in late pregnant rats (19-20 days of gestation). These changes in enzyme activity during pregnancy were associated with similar changes in the circulating levels of progesterone. The maximal activity and activity ratio (nu 0.5/V) were increased in male and female rats injected with progesterone. An increase in the total activity and activity ratio of mucosal PFK was also obtained in lactating rats. However, the enzyme was not strongly activated by inorganic phosphate, fructose 2,6-bisphosphate or glucose 1,6-bisphosphate either in early pregnant or lactating rats. These results indicate that mucosal PFK is already present as an active form during early pregnancy and lactation. Therefore, it is suggested that female sex hormones increase the circulating levels of insulin during early pregnancy which, in turn, positively affect the activity of mucosal PFK which could be also stimulated by the increased levels of fructose 2,6-bisphosphate. The increased activity of PFK in the peak lactating rats could be possible because of an increased demand for lactate production from glucose together with the stimulation of PFK by the increased concentrations of fructose 2,6-bisphosphate which therefore increases the rate of glycolysis.     

Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats

The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate k kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placent. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action.     

Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats

During baroreceptor unloading, sympathoexcitation is attenuated in near-term pregnant compared with nonpregnant rats. Alterations in balance among different excitatory and inhibitory inputs within central autonomic pathways likely contribute to changes in regulation of sympathetic outflow in pregnancy. Both baroreflex-dependent and baroreflex-independent GABAergic inputs inhibit sympathoexcitatory neurons within rostral ventrolateral medulla (RVLM). The present experiments tested the hypothesis that influence of baroreflex-independent GABAergic inhibition of RVLM is greater in pregnant compared with nonpregnant rats. Afferent baroreceptor inputs were eliminated by bilateral sinoaortic denervation in inactin-anesthetized rats. In pregnant compared with nonpregnant rats, baseline mean arterial pressure (MAP) was lower (pregnant = 75 +/- 6 mmHg, nonpregnant = 115 +/- 7 mmHg) and heart rate was higher (pregnant = 381 +/- 10 beats/min, nonpregnant = 308 +/- 10 beats/min). Pressor and sympathoexcitatory [renal sympathetic nerve activity, (RSNA)] responses due to bilateral GABA(A) receptor blockade (bicuculline, 4 mM, 100 nl) of the RVLM were greater in pregnant rats (delta MAP: pregnant = 101 +/- 4 mmHg, nonpregnant = 80 +/- 6 mmHg; delta RSNA: pregnant = 182 +/- 23% control, nonpregnant = 133 +/- 10% control). Unexpected transient sympathoexcitatory effects of angiotensin AT(1) receptor blockade in the RVLM were greater in pregnant rats. Although excitatory responses to bicuculline were attenuated by prior RVLM AT1 receptor blockade in both groups, pressor responses to disinhibition of the RVLM remained augmented in pregnant rats. Increased influence of baroreflex-independent GABAergic inhibition in RVLM could contribute to suppressed sympathoexcitation during withdrawal of arterial baroreceptor input in pregnant animals.     

Differential metabolic response to 48 h food deprivation at different periods of pregnancy in the rat

Since during pregnancy the mother switches from an anabolic to a catabolic condition, the present study was addressed to determine the effect of 48 h food deprivation on days 7, 14 and 20 of pregnancy in the rat as compared to age matched virgin controls. Body weight, free of conceptus, decreased with food deprivation more in pregnant than in virgin rats, with fetal weight (day 20) also diminishing with maternal starvation. The decline of plasma glucose with food deprivation was greatest in 20 day pregnant rats. Insulin was highest in fed 14 day pregnant rats, and declined with food deprivation in all the groups, the effect being not significant in 7-day pregnant rats. Food deprivation increased plasma glycerol only in virgin and 20 day pregnant rats. Plasma NEFA and 3-hydroxybutyrate increased with food deprivation in all groups, the effect being highest in 20 day pregnant rats. Food deprivation decreased plasma triacylglycerols in 14 day pregnant rats but increased in 20 day pregnant rats. In 20-day fetuses, plasma levels of glucose, NEFA and triacylglycerols were lower than in their mothers when fed, and food deprivation caused a further decline in plasma glucose, whereas both NEFA and 3-hydroxybutyrate increased. Liver triacylglycerols concentration did not differ among the groups when fed, whereas food deprivation caused an increase in all pregnant rats and fetuses, the effect being highest in 20-day pregnant rats. Lipoprotein lipase (LPL) activity in adipose tissue was lower in 20 day pregnant rats than in any of the other groups when fed, and it decreased in all the groups with food deprivation, whereas in liver it was very low in all groups when fed and increased with food deprivation only in 20 day pregnant rats. A significant increase in liver LPL was found with food deprivation in 20 day fetuses, reaching higher values than their mothers. Thus, the response to food deprivation varies with the time of pregnancy, being lowest at mid pregnancy and greatest at late pregnancy, and although fetuses respond in the same direction as their mothers, they show a specific response in liver LPL activity.     

Increased gluconeogenesis in the rat at term gestation

In this study the contribution of maternal gluconeogenesis to the glucose homeostasis of the maternal-fetal unit has been studied in fed term pregnant rats. We have measured the activity of two gluconeogenic enzymes, the rates of lactate turnover and the rates of gluconeogenesis from lactate in fed term pregnant rats. A decrease in plasma glucose and liver glycogen concentrations, and an increase of plasma lactate and alanine concentrations were observed in fed 22-day pregnant rats compared to virgin controls. Also, liver and kidney phosphoenolpyruvate carboxykinase activities and liver lactate dehydrogenase and hexose bisphosphatase activities significantly increased in fed term pregnant rats compared to virgin rats. The lactate turnover rate and the rate of gluconeogenesis in vivo from L-[U14C] Lactate increased four- and two-fold respectively in fed pregnant rats compared to fed virgins.     

Barium responsiveness of the rat aorta and femoral artery during pregnancy

The barium responses of isolated aortic strips and femoral arteries from non-pregnant and pregnant rats were investigated. Barium caused concentration-related increases in tension of vessels from both pregnant and non-pregnant rats. The concentration-response curves of femoral arteries from non-pregnant and 3 week pregnant rats were not different; however contractility and slopes of concentration-response lines for thracic aortas from 1, 2 and 3 week pregnant rats were significantly less than those of aortas from non-pregnant rats. In addition, barium caused rhythmic contractions to develop in both femoral arteries and aortas of 3 week pregnant rats more frequently than vessels from non-pregnant rats. Rhythmic contractions did not develop in aortas from 3 week pregnant rats rats in calcium-free Krebs. Since the effects of barium on the electrical and mechanical activity of various muscles have been postulated to be similar to and/or dependent on calcium, these results may indicate that changes in calcium sensitivity of vascular smooth muscle occur during pregnancy. Such changes may contribute to the blood flow redistribution and other cardiovascular adaptations of pregnancy.     

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.     

Effect of stress experienced during pregnancy on the rate of lipid peroxidation in erythrocytes and brain tissue of newborn rat pups

The rate of lipid peroxidation (LPO) in erythrocytes and brain homogenate has been assessed by the accumulation of malondialdehyde, the degree of erythrocyte autohemolysis, the content of hydrogen peroxide and catalase activity observed in newborn rats aged 1 hour, 1, 15, 20 and 30 days. Pregnant rats were exposed to emotional stress (aggressive interaction of two pregnant rats in an unavoidable conflict situation provoked by nociceptive irritation. Significant age-dependent differences in the rate of LPO (both in erythrocytes and cerebral tissue) have been found. The highest rate was noted in rats 15 days of age. The emotional stress of pregnant females resulted in the changes of behavioural reactions of newborn rats and LPO activity that was characterized by the increase in LPO rate in 1-hour- and 1-day-old rats and by slowing of LPO rate in 15-day-old rats. These phenomena were observed in erythrocytes and brain tissues of test animals.