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.     

Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.     

CONGENITAL SYPHILIS IN CALIFORNIA

Routine serologic tests for syphilis (as required by California law governing prenatal examination) and penicillin therapy during pregnancy for infected mothers have been major factors in the prevention of congenital syphilis in California during the past ten years. In 1940 one of each 822 infants had the disease, as indicated by morbidity reports of congenital syphilis in infants under the age of one year. In 1950 the ratio was one in 8,148. To determine why congenital syphilis continues to occur, a study of the 134 cases reported over a two-year period was made with the cooperation of local health officers and practicing physicians. It showed that in 76 per cent of cases the mother did not consult a physician prior to delivery or reported so late in pregnancy that the infant was born before adequate penicillin therapy could be given. In another 15 per cent syphilis developed in the mother during pregnancy after a negative reaction to a prenatal serologic test. The other 9 per cent of cases were due to various factors, such as infectious relapse or reinfection in previously adequately treated mothers. The study indicated that most cases occur in the lower socioeconomic population groups. Seventy-four per cent of cases were in infants delivered in county hospitals.     

Influence of rat prenatal and postnatal exposure to a non-steroidal anti-inflammatory agent (flunoxaprofen) on cardiovascular function in the progeny

The present experiments evaluated in rats the effects of prenatal and postnatal exposure to a non-steroidal antiinflammatory agent, flunoxaprofen (5-10 and 20 mg/kg/day by the oral route), on cardiovascular function in the pups. In both conscious and anaesthetized rats pre- and postnatal flunoxaprofen exposure at the 30th and 60th day of age, significantly (P less than .05) induced a decrease of pressor response to carotid-sinus baroreceptor stimulation and to L-noradrenaline (0.1-1 and 5 micrograms/kg iv), and an increase of the hypotensive responses to L-isoprenaline (0.01-0.1 and 1 microgram/kg iv) and acetylcholine (0.01-0.1 and 1 microgram/kg iv). These effects were not observed in rats on the 90th day of age. Moreover, pre- and postnatal flunoxaprofen exposure did not modify systolic arterial blood pressure of plasma levels of catecholamines and acetylcholinesterases. Our results also show that in normotensive rats flunoxaprofen exposure during pregnancy did not affect the body weight, systolic or diastolic blood pressure or heart rate of pregnant rats. It did not affect the length of gestation, number of pups per litter or pup body weight. No macroscopic teratogenic effects were observed.     

Effect of Acipimox on Plasma Lipids and Glucose/Insulin in Pregnant Rats

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (IV) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.     

Course of pregnancies in women with Cushing's disease treated by gamma-knife

Data concerning pregnancy in women with Cushing's disease treated by gamma-knife (GK) are scanty. We present and discuss the course and outcome of five pregnancies in two women with Cushing's disease (CD), the first of whom was treated only by GK, and the second one treated by surgery, GK and ketoconazole. In the first patient, pregnancy was uneventful and full-term. During gestation, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were steady, and always in the normal range for healthy non-pregnant individuals. The newborn was healthy and normal-weight. In the second woman, two pregnancies, occurring 3 years after GK and few months after ketoconazole withdrawal, were interrupted by spontaneous abortion or placental disruption despite normal cortisol levels. This patient became again pregnant 3 years later and delivered vaginally a healthy full-term infant. Seven months after the delivery, the patient became pregnant again and at the 39th week of gestation delivered vaginally a healthy male. Hypoprolactinemia and/or central hypothyroidism occurred in both cases. In women with CD treated by GK, pregnancy can occur. However, pregnancy is at risk even when ACTH and cortisol levels are normalized by treatment. After GK, evaluation of pituitary function is mandatory due to the risk of hypopituitarism.     

Pregnancy influence on the vascular interactions between nitric oxide and other endothelium-derived mediators in rat kidney

Peripheral vascular resistance and sensitivity to circulating pressor and vasoconstrictor agents are blunted during pregnancy. This has been mainly attributed to an increased production of endothelium-derived mediators. The objective of this work was to evaluate if pregnancy changes the relative participation of nitric oxide (NO) and prostaglandins (PG) in respect to the modulation of the increases in renal perfusion pressure induced by phenylephrine (Phe). Dose-response curves were made with gradually increasing doses of Phe using an isolated kidney preparation in the presence of a NO synthase (NOS) inhibitor (L-NAME, 1 microM), a PG-synthesis inhibitor (indomethacin, 1 microM), both, or neither. Also, renal cyclooxygenase (COX-1 and COX-2) and endothelial NOS (eNOS) expression was determined using PCR. The experiments were done in kidneys from nonpregnant and pregnant rats. Our results showed that the relative participation of renal vasoactive mediators seems to change during pregnancy. We found the presence of a COX-1-dependent vasoconstrictor in the middle of pregnancy that was not found in nonpregnant rats. Our results also suggest that there is increased participation of another renal vasodilator substance, the effect of which is observed when NO or PG synthesis is inhibited during late pregnancy. In addition, an apparent interaction between renal eNOS and COX-1 expression was observed: eNOS expression was diminished, while COX-1 was increased during the 2nd week of pregnancy. In contrast, in kidneys from the 3rd week of pregnancy, the expression of these two enzymes was similar.     

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.     

Progesterone is not responsible for the blood pressure fall in late-pregnant New Zealand genetically hypertensive rats

In various models of experimental and genetic hypertension in rats, blood pressure is markedly reduced during late pregnancy. The period during which the blood pressure reduction occurs is also the period when plasma progesterone is maximally elevated, and administration of progesterone to renal hypertensive rats has been reported to reduce blood pressure (J. Armstrong, 1959, Proc. Soc. Exp. Biol. Med. 102:452-455). To test the possibility that elevated plasma progesterone is responsible for the blood pressure reduction in late pregnancy, on Day 14 of pregnancy a group of New Zealand genetically hypertensive (NZGH) rats was ovariectomized and implanted with progesterone-filled capsules, to maintain plasma progesterone at low levels just sufficient to maintain pregnancy, and compared with intact, pregnant NZGH. Ovariectomy did not alter the characteristic course of blood pressure reduction seen in late-pregnant intact NZGH rats. In addition, daily administration of progesterone (15 mg/kg, sc) for 14 days did not alter blood pressure of either nonpregnant NZGH rats or New Zealand normotensive rats with chronic 1-kidney, 1-clip hypertension. It is concluded that blood pressure of NZGH rats is reduced to near normotensive levels in late pregnancy, as reported for other models of rat hypertension, but that elevated plasma progesterone levels are not requisite for that reduction and do not reduce blood pressure of renal hypertensive rats.     

Contraceptive use and efficacy in a genetically counseled population

Abstract

This paper reports contraceptive use and efficacy rates among 648 married women aged 15 to 44 who had received genetic counseling six months previously. Over half (53.5 per cent) of the counseled population were using non‐surgical contraception; 20 per cent were pregnant or postpartum; 10 per cent were seeking to become pregnant; 11 per cent were sterilized. Only 4.5 per cent were neither using contraceptives nor seeking to become pregnant. Women who were certain about their reproductive intentions after counseling utilized contraceptives effectively, with only two pregnancies at six months among those seeking to delay wanted pregnancies and only one pregnancy among those seeking to prevent pregnancy. This represents six‐month contraceptive failure rates of 4.3 and 2.1 per cent respectively for the two groups, rates similar to those with comparable intentions in the U. S. population at large. A distinguishing characteristic of the genetically counseled group was that 32 per cent of contraceptive users reported that their reproductive intentions were uncertain after counseling. The six‐month pregnancy rate in this uncertain group was 10 per cent.     

Essential hypertension and pregnancy.

Approximately 1% of pregnancies are complicated by essential hypertension. During pregnancy the blood pressure often stabilizes or improves. In patients with sustained hypertension, prospective controlled studies have demonstrated enhanced fetal survival when the blood pressure was controlled with antihypertensive medication. Such medication must be chosen carefully to avoid fetal and mateerial toxicity, and diuretics and salt restriction during pregnancy should be avoided. Among patients with essential hypertension the problem accelerates late in pregnancy in 2% to 11%; the acceleration may be predicted by determination of maternal mean arterial pressures and intravascular volumes early in pregnancy. The treatment of accelerated hypertension is identical to that of severe pre-eclampsia. Fetal loss is considerable but can be lessened by careful fetal and maternal monitoring and early controlled delivery. The risks of pregnancy in most patients with essential hypertension are small, and essential hypertension is not a uniform contraindication to pregnancy.     

The antihypertensive effect of U-0521 (3′,4′-dihydroxy-2-methylpropiophenone)

The synthetic catechol, U-0521, (3′,4′-dihydroxy-2-methylpropiophenone) is a competitive inhibitor of both tyrosine hydroxylase and catechol-O-methyltransferase. Continuous subcutaneous administration of 10 μmoles per day of U-0521 via Alzet osmotic minipumps to adult male Spontaneously Hypertensive Rats (SHR) reduced blood pressure from 160 mmHg to 125 mmHg. This effect occurred within two days, persisted for the two weeks that the pumps were in place, and reversed gradually upon cessation of U-0521 administration. Similar treatment of U-0521 to normotensive Wistar Kyoto rats (WKY) did not result in a similar hypotentensive effect. Subcutaneous administration of the same dose to juvenile SHRs led to a blockade in the expression of hypertension. After the five week treatment period, the blood pressure of the U-0521 treated animals escalated rapidly to match the saline treated controls. The antihypertensive effect of U-0521 on SHRs also occured when the compound was delivered by the oral route at the rate of 50 mg/kg/day.     

Single Administration of Ultra-Low-Dose Lipopolysaccharide in Rat Early Pregnancy Induces TLR4 Activation in the Placenta Contributing to Preeclampsia

Balanced immune responses are essential for the maintenance of successful pregnancy. Aberrant responses of immune system during pregnancy increase the risk of preeclampsia. Toll-like receptor 4 (TLR4) plays a crucial role in the activation of immune system at the maternal-fetal interface. This study aimed to generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist) administration on gestational day (GD) 5 as rats are subjected to placentation immediately after implantation between GDs 4 and 5, and to assess the contribution of TLR4 signaling to the development of preeclampsia. Single administration of 0.5 μg/kg LPS significantly increased blood pressure of pregnant rats since GD 6 (systolic blood pressure, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05) and urinary protein level since GD 9 (2.02 ± 0.29 mg versus 1.11 ± 0.18 mg, P < 0.01), but barely affected blood pressure or proteinuria of virgin rats compared with those of saline-treated pregnant rats. This was accompanied with adverse pregnancy outcomes including fetal growth restriction. The expression of TLR4 and NF-κB p65 were both increased in the placenta but not the kidney from LPS-treated pregnant rats, with deficient trophoblast invasion and spiral artery remodeling. Furthermore, the levels of inflammatory cytokines were elevated systemically and locally in the placenta from pregnant rats treated with LPS. TLR4 signaling in the placenta was activated, to which that in the placenta of humans with preeclampsia changed similarly. In conclusion, LPS administration to pregnant rats in early pregnancy could elicit TLR4-mediated immune response at the maternal-fetal interface contributing to poor early placentation that may culminate in the preeclampsia-like syndrome.     

Infusion of pregnant rats with calcitonin gene-related peptide (CGRP)(8-37), a CGRP receptor antagonist,increases blood pressure and fetal mortality and decreases fetal growth

Calcitonin gene-related peptide (CGRP) is the most potent endogenous vasodilatory peptide, and is involved in the regulation of blood flow to vital organs. We have previously shown that CGRP may be involved in vascular adaptations that occur during pregnancy, and that steroid hormones may be involved in these mechanisms. We hypothesized that endogenous CGRP is required for maintaining blood pressure and fetoplacental growth in pregnant rats, and that progesterone will enhance CGRP effects. The vasodilatory effects of CGRP are known to be inhibited by a competitive CGRP receptor antagonist, the C-terminal fragment CGRP(8-37). In the present study, we investigated whether continuous s.c. infusion of CGRP(8-37) to pregnant rats will reduce fetoplacental growth and increase systolic blood pressure. We also assessed whether progesterone will alter the effects of CGRP(8-37) on blood pressure during postpartum. Groups of five pregnant rats were s.c. infused with varying doses of CGRP(8-37) from Day 17 of pregnancy. Daily systolic blood pressures, pup weight, mortality at term delivery, and fetoplacental weights on Day 20 of gestation were measured. CGRP(8-37) at a dose of 0.083 mg day(-1) kg(-1) body weight (BW) showed no effects; however, doses of 0.33 and 1.33 mg day(-1) kg(-1) BW increased (P < 0.05) blood pressure during pregnancy, and these elevated blood pressures persisted during postpartum with the highest dose used. Progesterone (2 mg per injection, twice a day; s.c.) treatment significantly elevated blood pressure in rats infused with CGRP(8-37) during postpartum, suggesting that progesterone regulates CGRP-induced vascular effects. CGRP(8-37) infusion caused significant reductions in pup weight with an increase in mortality rate, and these effects were dose-dependent. Placental and fetal weights were also decreased prior to term on Day 20 of gestation, 72 h after CGRP(8-37) infusion, indicating effects on uteroplacental tissues. Therefore, we suggest that endogenous CGRP plays an important role in maintaining normal fetoplacental development, fetal survival, and vascular adaptations during pregnancy.     

Decidual reaction of the cervix; a review of 27 cases

Decidual reaction of the cervix is a benign growth produced by the hormones of pregnancy. These reactions or changes in the cervix are present in about 20 per cent of normal pregnant women. They may look like cancer but are not cancer. They are benign lesions. Bleeding is a common symptom and may occur at any stage of pregnancy. The presence of decidual reaction does not predispose to spontaneous miscarriage. In most cases no treatment is required; in a few light cauterization may be needed to control bleeding. Any suspicious lesion should be biopsied to rule out malignancy. By microscopic examination any experienced pathologist can differentiate a decidual reaction from cancer. The consensus of opinion is to let the pregnant woman deliver, normally, with this benign lesion, for it disappears after the baby is born. If cancer is found during pregnancy, it should be actively treated.     

Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin,a marinobufagenin antagonist

Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats.Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1–20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum.SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups.The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.     

Right atrial dimension-pressure relation during volume expansion is unaltered by pregnancy in the rat

Blood volume expands significantly during pregnancy, but afferent signals from cardiac receptors are reduced. In addition, during exogenous volume expansion, right atrial pressure (RAP) increases more for equivalent volumes in pregnant animals, implying reduced atrial compliance. To examine possible gestational alterations in atrial dimension during volume expansion, we compared the effects of volume expansion on RAP and right atrial dimension (RAD) in pregnant vs. virgin rats. Anesthetized animals were ventilated and catheterized for measurement of arterial pressure and RAP and for drug infusion. Through a parasternal incision, ultrasonic crystals were glued to the medial and lateral surfaces of the right atrium for measurement of RAD. Plasma volume and hematocrit were determined before experimentation. RAP, RAD, and arterial pressure were recorded at baseline and during progressive volume expansion (6% dextran, 60% of initial blood volume). Baseline RAP was similar in the two groups: 2.82 +/- 0.40 and 2.72 +/- 0.47 mmHg in pregnant and virgin rats, respectively. Basal RAD was significantly larger in pregnant than in virgin rats: 4.36 +/- 0.66 vs. 3.36 +/- 0.48 mm. Despite increased basal RAD in pregnant rats, the slope of the RAD-RAP relation during volume expansion was similar in the two groups. Results indicate that resting RAD is increased in pregnant rats and that the change in dimension during volume loads is similar to that in virgin rats. Thus, during pregnancy, the right atrium appears to accommodate the increased blood volume, and reduced afferent signaling most likely is due to mechanisms other than mechanical alterations of the atrium by expanded volume.     

Contraception of bison by GnRH vaccine: a possible means of decreasing transmission of brucellosis in bison

Preventing pregnancy in brucellosis-infected bison (Bison bison) provides a potential means of preventing transmission of disease. To determine whether a gonadotropin-releasing hormone (GnRH) vaccine was effective in reducing pregnancy in bison and to study the safety of injecting GnRH in pregnant bison, a study was conducted at the Idaho Fish and Game Wildlife Health Laboratory in Caldwell, Idaho (USA). Four pregnant and two nonpregnant female bison were given a single injection of GnRH vaccine, and five pregnant adult females were given a sham injection that contained only adjuvant. Three of the GnRH-vaccinated bison that were pregnant at the time of vaccination delivered healthy calves. One treated bison had dystocia that resulted in a dead calf. All control bison delivered healthy calves. After calving, females of both groups were exposed to two bulls. Treated bison were palpated 6 wk after exposure to the bulls, and blood was drawn for pregnancy-specific protein B analysis. The six treated bison were not pregnant. The sham-treated bison became pregnant and delivered viable calves. This study demonstrates that a single dose of GnRH vaccine is effective in preventing pregnancy in female bison for at least 1 yr.     

How obstetricians manage hypertension in pregnancy.

One thousand and ninety-three obstetricians answered a questionnaire on the management of pregnant women with pre-existing hypertension and pre-eclampsia. They reported that they frequently used antihypertensive drugs (most often methyldopa and diuretics) in severe essential hypertension but tended to give sedatives in mild cases. Renal impairment was considered more important that raised blood pressure as an indication for terminating pregnancy; but even without a raised blood urea concentration over a quarter of respondents (especially the more senior obstetricians) would have considered it. The more junior obstetricians were more likely to admit the least severely affected patients to hospital. Pre-eclampsia was usually treated with bed rest and sedatives (most frequently diazepam); but the choice of drug varied with the seniority of the respondents, the more senior obstetricians tending to confine themselves to the more familial drugs. There was considerable unanimity in the replies, even though most of the treatments and practices have not been validated by controlled trials, and two-thirds of the obstetricians gave the same answers to most of the questions.     

Progesterone mediated increase in monoamine stores and the regulation of enzymes of biosynthesis and metabolism in the adrenal gland during late pregnancy in the rat.

The influence of repeated injections of progesterone to pregnant rats upon monoamine storage and regulation of enzymes phenylethanolamine-N-methyltransferase (PNMT), monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) was studied. All the pregnant females received progesterone (4 mg/100 g body weight) on 19, 20 and 21 days post-coitum but one group was killed at 21 days of pregnancy and the other one at 0 h parturition. Adrenal epinephrine demonstrated highly significant increase in progesterone treated rats. At the same time norepinephrine content declined significantly from the control value. The activity of enzyme PNMT also showed marked increase in the adrenals of progesterone treated females. Activity of enzyme MAO showed a slight decline after progesterone treatment to pregnant rats. Enzyme COMT in progesterone treateed animals showed decline at 0 h parturition but at 21 days post-coitum it was significantly higher from non-injected females. All the increases and decreases in monoamines and the three enzymes were significant when the results were expressed per adrenal gland or per gram of adrenal. The results suggest that exogenous progesterone administration during late pregnancy increases epinephrine stores by declining monoamine metabolism by MAO and COMT and increasing their synthesis by PNMT which is responsible for N-methylation of norepinephrine to epinephrine.