The effects of estrogen on cortisol metabolism in female baboons

We examined Cortisol (F) dynamics in female baboons $\text{(Papio anubis)}$ treated with diethylstilbestrol (DES) or estradiol (E₂) and compared values with those previously measured in nonpregnant and pregnant animals. Five regularly menstruating baboons (12–18 kg, BW) were administered 5 mg DES daily via fruit or 0.5 mg E₂/0.1ml oil sc for 30 days. Blood samples, obtained before and after treatment, were assayed for serum F concentrations and serum Cortisol binding capacity (CBC). The metabolic clearance (MCR) and production rate (PR) of F and the catabolism of i.v. administered [³H] F were examined 25 and 30 days after initiation of estrogen treatment. Compared with values in nonpregnant baboons, F metabolism in estrogen treated animals is significantly altered and is characterized by increased formation of unconjugated metabolites, decreased glucuronylation, increased excretion of unconjugated F, cortisone, and highly polar metabolites, and increased CBC. These changes induced by estrogen are similar to those observed in intact pregnant baboons and permit the suggestion that the pattern of F metabolism and the level of CBC in baboon pregnancy are the result of elevated estrogen production.However, estrogen also caused a significant decrease in the MCR and PR of F, parameters which, by contrast, are similar in intact pregnant and nonpregnant baboons. These findings indicate that while estrogen also influences the rate of F clearance and F production, these effects of estrogen are not apparent during pregnancy. Collectively, these findings allow the suggestion that estrogen is a major factor which alters F metabolism and increases serum CBC in baboon gestation. However, additional factors are operative in primate pregnancy which maintain PR and MCR of F at levels similar to those of nonpregnant baboons.     

Cardiopulmonary reference standards in the pregnant sheep (Ovis aries): a comparative study of ovine and human physiology in obstetrics.

1. Complete blood counts, respiratory rate, tidal volume, arterial and mixed venous blood gases; heart rate, cardiac output, and arterial, pulmonary artery, central venous and pulmonary wedge pressures were determined in 10 pregnant adult sheep of 42.7-65.7 kg body weight. 2. Arithmetic means, standard deviations, and coefficients of variation were calculated to develop reference values; in addition, the 95% confidence limits for ranges were established. 3. Comparison of derived data with that from non-pregnant sheep shows changes similar to those seen when examining pregnant and non-pregnant humans. 4. These results indicate the pregnant sheep is an acceptable model for human obstetrical research.     

Reference standards and the physiologic significance of the pregnant goat (Capra hircus) as a human model in obstetrical research

1. Amniotic fluid, cerebrospinal fluid, serum, and urine chemistries; respiratory rate and arterial and mixed venous blood gases; heart rate, hematocrit, and cardiac output; and arterial, pulmonary artery, central venous and pulmonary wedge pressures were measured in 20 pregnant adult goats of 19.5-34 kg body weight. 2. Arithmetic means, standard deviations, and coefficients of variation were calculated to develop reference values; in addition, the 95% confidence limits for ranges were established. 3. Comparison of derived data with that from non-pregnant goats shows changes similar to those seen when examining pregnant and non-pregnant humans. 4. These results indicate the pregnant goat is an acceptable model for human obstetrical research.     

Increased Na+ intake during gestation in rats is associated with enhanced vascular reactivity and alterations of K+ and Ca2+ function

Gestation is associated with decreased blood pressure and resistance to the effects of vasoconstrictor agents. A recent study showed that pregnant rats, on increased sodium intake, present physiological changes that resemble those observed in preeclampsia. We investigated the effects of sodium supplementation on reactivity and on potassium and Ca(2+) channel activity in blood vessels during gestation. Sodium supplements, 0.9% or 1.8% NaCl as drinking water, were given to nonpregnant and pregnant rats for 7 days (last week of gestation). Reactivity to phenylephrine (PE), KCl, arginine vasopressin (AVP), and tetraethylammonium (TEA) was measured in aortic rings under modulation of potassium and calcium channels. TEA, a nonselective K(+) channel inhibitor, induced concentration-dependent responses in aortic rings from nonpregnant but not in those from pregnant rats. The response to TEA was restored in rings from pregnant rats after preincubation with 10 mmol/l KCl. Sodium supplementation did not affect the response to TEA in the aortas of pregnant animals. After sodium supplementation, maximum responses to PE and AVP were decreased and increased in aortic rings from nonpregnant and pregnant rats, respectively. Cromakalim (an ATP-sensitive K(+) channel activator)-induced inhibition of the responses to the three vasoconstrictors was more striking in aorta from nonpregnant than pregnant rats on regular diet, whereas it produced similar inhibition in tissues from both groups of animals on 0.9% and 1.8% NaCl. NS-1619 (a Ca(2+)-sensitive K(+) activator) elicited heightened effects in the aortas of pregnant animals receiving 0.9% NaCl supplementation. Nifedipine (a Ca(2+) channel blocker) caused greater inhibition of the contractile responses in tissues from nonpregnant rats on regular diet, and its action was increased in pregnant rats on sodium-supplemented diets. These data demonstrate that augmented sodium intake during gestation in the rat is linked with the reversal of gestational-associated resistance to vasopressors and indicate that this is an experimental model showing some features of gestational hypertension.     

Determination of cardiac output and other reference physiology parameters in lightly anesthetized dogs

1. Cardiac output; arterial, pulmonary artery, central venous and pulmonary wedge pressures; heart rate, hematocrit, and plasma sodium and potassium; arterial and mixed venous blood gases; and respiratory rates were measured in 45 mixed sex, non-pregnant, clinically normal mongrel dogs of 8-30 kilograms body weight following light anesthesia with halothane/50% N20-02. 2. Arithmetic means and standard deviations were calculated to develop tables of reference values. 3. Mean measured cardiac outputs were found to be 31-59% higher in these dogs than the values indicated by published standards; cardiac indices were 30-44% higher; heart rates were 16-30% lower; calculated stroke volumes were 60-112% greater; and total peripheral resistances were 35-57% less than the standard published values. 4. All other measured or calculated parameters fell within previously published canine or human reference limits.     

Effect of pregnancy, postnatal growth, and gender on renal sulfate transport.

Serum sulfate concentrations are increased in infants, young children, and pregnant women, compared with adult values. The objective of this investigation was to examine the influences of age, gender, and pregnancy on renal sulfate transport using guinea pigs as an animal model. Membrane vesicles were isolated from the kidney cortex of male animals at four different ages, from male and female adult animals, and from pregnant and nonpregnant female animals. There were no significant differences in marker enzymes for the brush-border membrane (BBM) or basolateral membrane (BLM) among all groups examined. Uptake was determined by a rapid filtration method and membrane fluidity by measuring the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene. The Vmax values for Na+ /sulfate co-transport in BBM were significantly increased with decreasing age, whereas the Km for this process was unchanged. The Vmax and Km for Na + /sulfate co-transport in BBM of pregnant animals were significantly higher than the values in the nonpregnant group. Bicarbonate-driven anion exchange of sulfate in BLM was not different among the different age groups. The Vmax for the bicarbonate/sulfate exchange process in BLM was not different between pregnant and nonpregnant groups; however, the Km for this process in BLM of pregnant animals was significantly greater than the value in nonpregnant animals. There were no gender-related differences in sulfate transport in BBM or BLM isolated from adult male and female animals. Renal BBM fluidity was increased with decreasing age and in pregnant animals, suggesting that altered membrane fluidity may represent one possible mechanism to explain the increased sodium/sulfate uptake in young and pregnant animals. The higher Vmax for Na+/sulfate co-transport in young and pregnant animals suggests that there is an increased density of co-transporter protein or an increase in the rate of movement of the carrier protein (i.e., turnover) once loaded with sodium and sulfate. This increased conservation of inorganic sulfate in young and pregnant guinea pigs may be related to the increased demand for sulfated substrates, such as sulfated glycosaminoglycans, during growth and development.     

Prostaglandin E2 and gestational hypotension in rabbits

Arterial levels of 13,14-dihydro-15-keto-PGE2 (PGE2-M), a stable metabolite of prostaglandin E2 (PGE2) were compared between unanesthetized pregnant (n = 12) and nonpregnant (n = 8) rabbits with the aim of elucidating the role PGE2 in the development of physiological hypotension associated with pregnancy. On the 20th and 22nd days of the 30 day gestation period the mean arterial concentrations of PGE2-M were about 10-times higher (p less than 0.05) and largely variable as compared to that of nonpregnant rabbits. Mean arterial pressure was not lower on either the 20th (69 +/- 4 mmHg, mean +/- SD) or the 22nd (70 +/- 3 mmHg) days of gestation (dg) than in nonpregnant rabbits (69 +/- 4 and 73 +/- 6 mmHg, respectively). On the 23rd dg hypotension was invariably present (61 +/- 5 mmHg vs 72 +/- 4 in nonpregnants, p less than 0.001), but arterial levels of PGE2-M (31.0 +/- 31.6 ng/ml) did not overcome those measured on earlier, normotensive days of gestation. Hypotension was also evident in a subgroup of pregnant rabbits (n = 4) with low PGE2-M concentrations in the nonpregnant range (3.2 +/- 1.5 ng/ml vs 1.9 +/- 1.2 in nonpregnant rabbits, ns). Since the arterial level of PGE2-M proved to correlate (p less than 0.001) with both the uteroplacental venous and renal venous PGE2 concentrations, we suggest that a key role of uteroplacental and renal PGE2 played in the development of gestational hypotension is not probable in rabbits.     

Maternal hypoxic ventilatory response, ventilation, and infant birth weight at 4,300 m

To test the hypothesis that increased hypoxic ventilatory responsiveness (HVR) raised maternal ventilation and arterial oxygenation during high-altitude pregnancy and related to the birth weight of the offspring, we studied 21 residents of Cerro de Pasco, Peru (4,300 m), while eight of them were 36 +/- 0 wk pregnant and 15 of them 13 +/- 0 wk postpartum. HVR was low in the nonpregnant women (mean +/- SE shape parameter A = 23 +/- 8) but increased nearly fourfold with pregnancy (A = 87 +/- 17). The increase in HVR appeared to account for the 25% rise in resting ventilation with pregnancy (delta VE observed = 2.4 +/- 0.7 l/min BTPS vs. delta VE predicted from delta HVR = 2.6 +/- 1.7 l/min BTPS, P = NS). Hyperoxia decreased ventilation in the pregnant women (P less than 0.01) to levels similar to those measured when nonpregnant. The increased ventilation of pregnancy raised arterial O2 saturation (SaO2) from 83 +/- 1 to 87 +/- 0%, and SaO2 was correlated positively with HVR in the pregnant women. The rise in SaO2 compensated for a 0.9 g/100 ml decrease in hemoglobin concentration to preserve arterial O2 content at levels present when nonpregnant. Cardiac output in the 36th wk of pregnancy did not differ significantly from values measured postpartum. The increase in HVR correlated positively with infant birth weight. An increase in HVR may be an important contributor to increased maternal ventilation with pregnancy and infant birth weight at high altitude.     

Effect of uncomplicated pregnancy on body water content and distribution in baboons

Body water content and distribution were estimated before, during, or after 32 pregnancies in baboons. Water content of the various compartments (in liters) correlated with body weight in both nonpregnant and pregnant baboons, and with length of gestation in pregnant baboons. In proportion to body weight (in ml/kg), most water compartments did not change significantly with length of gestation. Mean plasma volume and blood volume were higher during pregnancy than before or after.     

Progesterone Levels During Pregnancy in the Greater Thick-tailed Galago (Galago crassicaudatus)

Serum progesterone concentrations in Galago crassicaudatus were quantified at 3-week intervals throughout the 136-day pregnancy. Progesterone concentrations were significantly elevated over those of nonpregnant controls as early as 6 weeks after conception. Progesterone continued to increase throughout gestation. The progesterone profile in pregnant G. crassicaudatus quantitatively resembles that of chimpanzees and qualitatively resembles that of humans. In two animals that aborted, progesterone concentrations after abortion decreased to values comparable to those seen in nonpregnant animals.     

Serum cortisol levels affect the metabolic clearance rate of progesterone in female baboons.

Since interactions between progesterone (P₄), Cortisol (F), cortisone (E) and corticosteroid binding globulin (CBG) may influence the metabolic clearance rates (MCR) of these steroids, the effect of altering circulating F concentrations on clearance of the steroids was determined. MCR of P₄, F and E were determined by the iv constant infusion method in 6 pregnant and 6 nonpregnant baboons (Papio papio). Serum F concentrations were altered by iv infusion of 5 mg F/90 min or im injection of betamethasone (3 mg bi-daily for 2 days). Mean MCR-P₄ (1/d/kg ± SE) was greater (P < 0.01) in pregnant (92.8 ± 8.5) than in nonpregnant (53.9 ± 4.4) animals while mean MCR-F was similar in both groups ($\text{10.8 ± 1.2}\text{vs}\text{13.0 ± 1.5}$, respectively). Mean MCR-E was also similar in pregnant (30.8 ± 4.9) and nonpregnant (34.1 ± 4.5) baboons. Mean serum F concentrations (/gmg/100 ml ± SE) in 4 nonpregnant (42.0 ± 8.6) and 4 pregnant (52.2 ± 10.0) baboons were increased (P < 0.05) 60% by F administration but MCR-P₄, -F and -E were unaltered. Betamethasone treatment reduced (P < 0.05) serum F 75% in both groups. In nonpregnant baboons, betamethasone treatment reduced (P < 0.01) MCR-P₄ (37.3 ± 3.9), MCR-F (7.4 ± 1.6) and MCR-E (18.5 ± 3.7). Betamethasone treatment of pregnant animals reduced (P < 0.01) MCR-P₄ (56.5 ± 7.4), MCR-F (6.3 ± 0.8) and MCR-E (14.6 ± 2.6). Infusion of F into betamethasone-treated animals increased serum F levels and increased MCR-P4, -F and -E. It is concluded that variations in serum F levels affect the clearance of F, E and P₄ presumably because of the mutual interactions of these steroids with CBG.     

Hemodynamics of conscious unrestrained baboons, including cardiac output

A method is described for comprehensive hemodynamic study of undisturbed baboons (Papio hamadryas) that incorporates cardiac output measurement by thermodilution. Instrumentation includes arterial, aortic, and central venous catheterization by a surgical technique that does not require entry to peritoneal or thoracic cavities. It provides a means for right atrial indicator delivery with aortic temperature recording of thermodilution curves. Accuracy was confirmed by comparison to measurement by Swan-Ganz catheters. Diurnal variations of systemic arterial pressure in long-term study of conscious baboons were shown to result from significant increases in cardiac output by day (P less than 0.001), despite concomitant falls in systemic vascular resistance. The cardiac output values obtained were 0.13 l.min-1.kg-1 at night and 0.16 l.min-1.kg-1 by day. Comparison of these results to previous reports of cardiac output in baboons highlights the inadequacies of methods that require physical restraint or anesthesia. This technique also leaves the baboons intact for subsequent breeding or experimental use after catheter removal without the need for further surgery.     

Serum leptin in nonpregnant and pregnant women and in old and new world nonhuman primates

Leptin is a hormone that is produced during mammalian pregnancy in the placental trophoblast and other tissues, including! fetal and maternal adipocytes. Synthesis of the polypeptide and the presence of its specific receptors throughout the human maternal fetoplacental unit suggest direct effects on conceptus growth and development. However, both the physiologic roles of leptin and the mechanisms regulating leptin synthesis in human pregnancy differ from those in laboratory and domestic species, necessitating the development of non-human primate research models. Therefore, we compared serum leptin concentrations in nonpregnant and pregnant women with those in both old world nonhuman primates (i.e., baboon, rhesus monkey, cynomolgus monkey) and new world nonhuman primates (i.e., squirrel monkey, titi monkey). As expected, maternal leptin levels were elevated in human and baboon pregnancies (P < 0.05 and P < 0.001, respectively). Levels in both species of old world monkeys were also greatly enhanced (P < 0.001). Although maternal serum concentrations were slightly elevated compared to nonpregnant levels in both species of new world monkeys, overall concentrations were dramatically lower than for either old world primates or humans. Results provide comparisons of serum leptin concentrations in pregnant and nonpregnant humans and baboons with those in both old and new world monkeys and further characterize these nonhuman primates as models for the investigation of leptin dynamics in pregnancy.     

A comparative and regional study of potassium induced relaxation of vascular smooth muscle

Summary The current study was undertaken to assess species and regional variations in the relaxation of vascular smooth muscle in response to potassium and in the ouabain sensitivity of this relaxation. The effect of species variation was investigated through the use of tail arteries from rats, dogs, cats, monkeys, and pigs; the effect of regional variation was studied in tail, middle cerebral, femoral, and posterior coronary arteries from baboons. Helical strips from all of these vessels were made to contract with norepinephrine or serotonin in a potassium-free solution. The vessels relaxed when potassium was added back to the solution. Strips of tail artery from rats, dogs, and monkeys showed greater relaxation in response to potassium than did strips from pigs and cats. Helical strips from tail, cerebral, and coronary arteries of the baboon relaxed to a greater degree in response to potassium than did strips from the femoral artery. Ouabain produced a concentration-dependent decrease in the magnitude of potassium relaxation in all vessel types. Half-maximal inhibition occurred at approximately 10^–8 to 10^–7 M in all arterial strips except those obtained from rat tail artery (5×10^–5 M). The inhibition of potassium relaxation by ouabain was fully reversed by 30 min exposure to a ouabain-free solution in only the rat tail artery strips. A component of potassium-induced relaxation in tail artery strips from monkeys and baboons was not inhibited by ouabain. The results show that the magnitude of response, potassium and ouabain sensitivity, and recovery from ouabain treatment of potassium relaxation are species related. The regional bed from which the vascular smooth muscle is derived also determines the magnitude and potassium sensitivity of the relaxation. These parameters of potassium-dependent relaxation may reflect corresponding differences in the electrogenic pumping of sodium and potassium among various animal species and various regional vascular beds.Abbreviations ATPase adenosine triphosphatase - PSS physiological salt solution - C contractile magnitude from baseline in milligrams - R relaxation measured as residual force above baseline in milligrams - SEM standard error of the mean These studies were supported by NHLBI grant HL-18575Dr. Webb was a Post-doctoral Research Fellow of the Michigan Heart Association during this investigation     

Geophagy in chacma baboons: patterns of soil consumption by age class, sex, and reproductive state

Despite baboons' widespread distribution across Africa, geophagy among all subspecies has been poorly documented. We used video camera traps and soil analyses to investigate geophagy in chacma baboons (Papio cynocephalus ursinus) inhabiting the Western Cape of South Africa. During an 18‐month study, from August 2009 to January 2011, we continually monitored the largest and most frequently visited geophagy sites with camera traps for 545 days and captured soil consumption at one or more sites on 266 of those days (49%). In 3,500 baboon visits to geophagy sites, video camera traps captured 58.6 hr of geophagy. From these data, we evaluated site preference based on time spent consuming soil among these four geophagy sites. One hundred and seventy days of soil consumption data from the most frequently visited geophagy site allowed us to look for demographic trends in geophagy. Selected consumed soils from geophagy sites were analyzed for mineral, physical, and chemical properties. The baboons spent more time consuming white alkaline soils with high percentages of clay and fine silt, which contained higher concentrations of sodium than non‐white acidic soils that contained higher concentrations of iron. Our data indicate that pregnant chacma baboons spent more time consuming soil at monitored geophagy sites than baboons of any other age class, sex, or reproductive state. Based on analytical results, the soils consumed would be effective at alleviating gastrointestinal distress and possibly supplementing minerals for all age/sex classes, but potentially for different age/sex requirements. Am. J. Primatol. 74:48–57, 2012. © 2011 Wiley‐Liss, Inc.     

Biochemistry and haematology values for the baboon (Papio hamadryas): the effects of sex, growth, development and age.

A retrospective study evaluated the influence of sex and age on plasma biochemistry and haematology parameters in a captive-bred colony of baboons. Over 1,140 ETDA and heparin blood samples were obtained from 160 clinically normal baboons between the ages of 11 months and 11 years. Data for these blood tests were analysed for the effects of sex, age and sex age interactions. Sex, age and sex age interactions were detected for many plasma biochemistry and haematological parameters. The reference range values for platelets, white-blood cells and mean corpuscular volume and plasma chloride, glucose, total protein and iron were higher (P < 0.01) and red blood cell, plasma sodium, potassium, total CO2, creatinine, urea, total bilirubin, albumin, alkaline phosphate, gamma glutamyl transpeptidase and phosphate were lower (P < 0.01) in the female compared to the male population. Sex age interactions (P < 0.05) were seen with haemoglobin, white blood cells, haematocrit, mean corpuscular volume, sodium, creatinine, urea, calcium, phosphate, total bilirubin, total protein alkaline phosphatase, the liver enzymes and triglycerides. Plasma alkaline phosphatase was highest ( > 800 micro/l) in young juveniles of both sexes; creatinine was higher in older ( > 4 years) compared to younger baboons of the same sex (P < 0.05). Plasma cholesterol and triglycerides were greater (P < 0.01) in young baboons compared to older animals.     

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.     

Haemodynamics using transthoracic echocardiography in healthy pregnant and non-pregnant baboons (Papio hamadryas)

Background To determine systolic and diastolic function using transthoracic echocardiography in the baboon (Papio hamadryas). Methods Transthoracic echocardiography was performed in eight non‐pregnant female and six pregnant baboons according to American Society of Echocardiography recommendations. Results Haemodynamic measurements were obtained from fourteen baboons. Compared to non‐pregnant baboons, pregnant baboons demonstrated: (mean ± SD, pregnant vs. healthy) increased cardiac output (1615 ± 121 ml/minutes vs. 1317 ± 134 ml/minutes P = 0.001) due to an increased heart rate [120 ± 11 beats per minute (BPM) vs. 105 ± 6 BPM P = 0.018]. The inter‐observer and intra‐observer variability (mean difference ± SD) for the left ventricular outflow tract diameter was 0.05 ± 0.07 cm and 0.01 ± 0.03 cm respectively. There was minimal impact to the animal’s daily activities. Conclusions Transthoracic echocardiography was applicable and reproducible for the assessment of haemodynamics in baboons thus enabling translation of animal results to human studies.     

Plasma protein carbonyls in nonpregnant,healthy pregnant and preeclamptic women

Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women.

Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy non-pregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis.

Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls.

The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia.     

Influence of pregnancy on mean systemic filling pressure and the cardiac function curve in guinea pigs.

To assess the degree of circulatory fullness and to evaluate the influence of peripheral and cardiac factors in the regulation of cardiac output during pregnancy, the following studies were conducted using pentobarbital-anesthetized, open-chest nonpregnant and late term pregnant guinea pigs. Mean circulatory filling pressure was taken as the equilibrium pressure when the pulmonary artery was constricted. Total vascular compliance was assessed by +/- 5-mL changes in blood volume performed while this constriction was maintained. A separate group of guinea pigs was prepared with a pulmonary artery electromagnetic flow probe and right atrial catheter. Rapid infusion of saline was used to increase right atrial pressure while the cardiac output was determined. Pregnancy was characterized by the following changes relative to nonpregnant controls: 51Cr-labelled RBC blood volume increased from 55 +/- 3 to 67 +/- 3 mL/kg; mean circulatory filling pressure increased from 7.1 +/- 0.2 to 8.0 +/- 0.5 mmHg (1 mmHg = 133.322 Pa); right atrial pressure decreased from 3.4 +/- 0.2 to 2.1 +/- 0.3 mmHg; and cardiac output increased from 71.8 +/- 3.9 to 96.8 +/- 3.3 mL.min-1.kg-1. Total vascular compliance was not changed (2.1 +/- 0.1 mL.kg-1.mmHg-1) and most of the expanded blood volume was accommodated as unstressed volume. The cardiac function curve was shifted upwards in pregnant animals. The resistance to venous return, as determined from the slope of the venous return curves, was not changed. These data suggest that the circulation of the pregnant guinea pig is slightly overfilled.(ABSTRACT TRUNCATED AT 250 WORDS)