RESUMO
OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.
Assuntos
Pré-Eclâmpsia/urina , Resultado da Gravidez , Proteinúria/diagnóstico , Adulto , Estudos de Coortes , Creatinina/urina , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez , Estudos Prospectivos , Curva ROC , Fitas Reagentes , Fatores de Risco , Coleta de Urina/métodosRESUMO
The role of augmented aldosterone production in pregnancy is poorly understood. Whereas some consider aldosterone secretion in pregnancy excessive, others suggest that this is a compensatory phenomenon. According to yet another view, mechanisms other than the renin-angiotensin-aldosterone system control sodium homeostasis in pregnancy. Metabolic balance studies were performed on 14 3rd trimester women. Mineralocorticoid activity was experimentally increased by administering desoxycorticosterone acetate, 9alpha-fluorocortisol acetate, or ACTH for 4-12 days. Administration of mineralocorticoid or ACTH consistently caused sodium retention. During this mineralocorticoid-induced volume expansion, aldosterone excretion decreased markedly. Natriuresis, which followed discontinuance of the drug, continued while aldosterone excretion, although greatly diminished compared to control values, was greater than that found in normal, nonpregnant individuals. This saline diuresis did not subside until aldosterone excretion returned to its previously high control values. These observations support the concept of the physiological role of increased aldosterone production in pregnancy. Results further revealed a marked dissociation between antinatriuretic and kaliuretic effects of corticoids. Potassium balance was virtually unaltered during continued mineralocorticoid or ACTH administration, despite initially high or abruptly increased sodium intakes. Finally, mineralocorticoid escape was induced by continued desoxycorticosterone acetate therapy in two male volunteers. Kaliuresis occurred which was subsequently abolished when progresterone was administered. Sodium excretion, however, was virtually unaltered. These data, mimicking results observed in gravidas, suggest that progesterone is an important determinant of potassium homeostasis in pregnant women.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Desoxicorticosterona/farmacologia , Fludrocortisona/farmacologia , Mineralocorticoides/fisiologia , Potássio/urina , Gravidez , Adolescente , Adulto , Aldosterona/urina , Ensaios Clínicos como Assunto , Creatinina/urina , Depressão Química , Feminino , Humanos , Túbulos Renais/fisiologia , Masculino , Natriurese , Progesterona/farmacologia , Equilíbrio HidroeletrolíticoRESUMO
The relationship between net tubular reabsorption of sodium and renal microsomal sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) was evaluated in hypothyroid and hyperthyroid rats and in age-matched euthyroid controls. Tubular sodium reabsorption per gram of kidney was lower in thyroidectomized rats than in controls (186+/-14 vs. 246+/-12 mueq/min; P < 0.005) and was accompanied by a quantitatively similar reduction in Na-K-ATPase specific activity (49.4+/-2.4 vs. 65.8+/-2.3 mumol inorganic phosphate (P(t))/mg protein per h; P < 0.001). This decrement was present in both cortex and outer medulla, and was limited to Na-K-ATPase since other representative enzymes not involved in sodium transport (magnesium-dependent adenosine triphosphatase [Mg-ATPase], glucose-6-phosphatase, 5'-nucleotidase) remained unchanged or increased in the hypothyroid animals. Conversely, Na-K-ATPase rose when sodium reabsorption increased in euthyroid rats treated with triiodothyronine. Subsequent experiments were performed to determine to what extent the decrease in Na-K-ATPase is due to lack of thyroid hormone per se or to an adaptive response to decreased reabsorptive sodium load. Triiodothyronine in concentrations of 10(-12) to 10(-5) M had no effect in vitro on microsomal Na-K-ATPase of either thyroidectomized or euthyroid rats. When hypothyroid rats were uninephrectomized or treated with methylprednisolone, sodium reabsorption per gram kidney increased markedly and was similar to that of intact controls. Despite persistence of the hypothyroid state, Na-K-ATPase specific activity also increased to levels not significantly different from euthyroid animals. These data suggest that decreased tubular sodium transport is a major determinant of the reduction in renal Na-K-ATPase in thyroid deficiency since the latter can be reversed by increasing sodium reabsorption during continuing hypothyroidism. Furthermore, the modest sodium leak of hypothyroid animals does not appear to be due to decreased Na-K-ATPase since it was not corrected by uninephrectomy despite restoration of both cortical and medullary Na-K-ATPase activity to normal by this maneuver. The close correlation between net sodium reabsorption and Na-K-ATPase in all the experimental situations described here demonstrates that renal Na-K-ATPase changes adaptively in hyper- or hypothyroidism as it does in numerous situations in the normal animal, in accord with its postulated role in the active transport of sodium across the renal tubule.
Assuntos
Adenosina Trifosfatases/metabolismo , Hipotireoidismo/enzimologia , Rim/enzimologia , Sódio/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Feminino , Glucose-6-Fosfatase/metabolismo , Hipertireoidismo/enzimologia , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Isótopos de Iodo , Rim/citologia , Túbulos Renais/metabolismo , Metilprednisolona/farmacologia , Microssomos/enzimologia , Nefrectomia , Nucleotidases/metabolismo , Potássio , Ratos , Glândula Tireoide/fisiologia , Tireoidectomia , Tri-Iodotironina/farmacologiaRESUMO
Mineralocorticoid-treated, normotensive third trimester subjects positioned in lateral recumbency were studied before and during the infusion of 300 mEq of hypotonic saline. Urinary sodium excretion increased in all subjects from a mean value of 199 to 416 muEq/min. In 12 maximally hydrated subjects free water clearance (C(H2O)) and urine flow (V) increased from means of 7.54 and 9.50 to 11.6 and 14.5 ml/100 ml of glomerular filtrate (GFR) Also the ratio of urea to inulin clearance (C(urea)/C(inulin)) increased from 0.59 to 0.64. The changes in the renal handling of water and urea suggest that fractional sodium reabsorption decreased at proximal nephron sites. The subjects then assumed a supine position, and the results were compared to those obtained during the lateral recumbent control periods. Filtered sodium decreased in 11 experiments, but in five studies it remained up to 2.6 mEq/min above control values. There was only one instance in which a significant increase in sodium excretion occurred. It was concluded that supine recumbency blunts natriuresis despite volume expansion or an increase in the filtered load of sodium.Finally, in the 12 hydrated subjects supine recumbency reduced C(H2O) and V from a mean of 11.6 and 14.5 to 6.2 and 8.2 ml/100 ml of GFR. In eight of these experiments urine osmolality fell or did not change. Simultaneously, C(urea)/C(inulin) fell from 0.64 to 0.57. These data suggest that the antinatriuresis, which occurred when the volume-expanded subjects were positioned in supine recumbency, was accompanied by a decrease in the fractional reabsorption of sodium at proximal nephron sites.
Assuntos
Diurese , Soluções Hipotônicas/administração & dosagem , Rim/fisiologia , Natriurese , Postura , Gravidez , Ureia/urina , Adulto , Transporte Biológico , Feminino , Humanos , Testes de Função Renal , Túbulos Renais/fisiologia , Potássio/urina , Sódio/sangue , Sódio/metabolismo , Equilíbrio HidroeletrolíticoRESUMO
We previously observed that osmoregulation and the osmotic threshold for antidiuretic hormone secretion were altered during pregnancy in Sprague-Dawley rats and the present study evaluated the influence of volume on arginine vasopressin (AVP) release during gestation in this species. Basal plasma osmolality (Posm) and intravascular volume were 297 +/- 3 mosmol/kg and 16.2 +/- 1.2 ml in virgin animals compared with 290 +/- 2 mosmol/kg and 20.2 +/- 2.3 ml in 14-d pregnant rats and 287 +/- 3 mosmol/kg and 25.2 +/- 2.3 ml in 21-d (near-term) pregnant rats (P less than 0.001, each pregnant group vs. virgin). Isosmotic volume depletion was produced by intraperitoneal polyethylene glycol. Volume decreased from 1 to 26% and blood pressure remained stable during decrements as high as 16%. Plasma AVP (PAVP) did not rise significantly in either group of pregnant animals or virgin controls until blood volume depletion reached 6-7%, after which levels rose in a similar exponential manner in virgin, 14-d, and 21-d pregnant animals. In terms of absolute changes, however, PAVP in gravid rats started to increase when intravascular volume was still considerably greater than basal blood volume in the nonpregnant controls. Other experiments, where Posm was increased by intraperitoneal hypertonic saline, reconfirmed that the osmotic threshold for AVP secretion was reduced congruent to 10 mosmol/kg during pregnancy and that AVP release was stimulated by increments in body tonicity as small as 1-2%. In parallel studies, blood volume contraction and increases in Posm were evoked by intraperitoneal polyethylene glycol dissolved in hypertonic saline and results compared with animals receiving intraperitoneal saline alone. Decrements in volume (congruent to 7%), which alone would increase PAVP minimally, increased the sensitivity of the secretory response to changes in osmolality two- to three-fold, an effect which was similar in virgin and gravid animals. Finally, restricting water intake of pregnant rats to that of virgins on days 16-20 of gestation led to suboptimal volume expansion, hypertonicity, and an exaggerated increase in PAVP. These results demonstrate that despite an intravascular space which at term is nearly twice that of virgin rats, pregnant animals secrete AVP in response to fractional volume depletion in a manner similar to nonpregnant controls; that is, the relationship between total blood volume and AVP secretion is altered during gestation such that the expanded blood volume is recognized as normal.
Assuntos
Arginina Vasopressina/metabolismo , Volume Sanguíneo , Prenhez , Animais , Arginina Vasopressina/sangue , Pressão Sanguínea/efeitos dos fármacos , Volume Sanguíneo/efeitos dos fármacos , Peso Corporal , Eritrócitos/fisiologia , Feminino , Masculino , Concentração Osmolar , Polietilenoglicóis/farmacologia , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Osmoregulation was studied in near term and age-matched Sprague-Dawley rats. Basal plasma osmolality (P(osm)) and plasma sodium (P(Na)) were 281+/-3 mosmol/kg and 134+/-3 meq/liter, respectively, on the 20th gestational day compared with 292+/-3 mosmol/kg and 140+/-1 meq/liter in virgin animals (P < 0.001), whereas P(urea) and plasma water content were similar in pregnant and control rats. These differences could not be reproduced in animals receiving progesterone, estrone, or a combination of progesterone and estradiol for 2 wk. Pregnant and control rats were deprived of water for periods ranging from 0 to 48 h. P(osm), always lower in gravidity, was 290+/-3 mosmol/kg after 2 d of water deprivation in pregnant animals compared with 300+/-2 mosmol/kg in controls (P < 0.001). Thus 48 h of dehydration were required before P(osm) in gravid rats was similar to basal values in the age-matched virgins. Despite strikingly lower P(osm), plasma arginine vasopressin (P(AVP)) and urinary osmolality (U(osm)) were similar in the basal state averaging 2.16+/-0.78 pg/ml and 1,652+/-406 mosmol/kg, respectively, during pregnancy compared with 2.08+/-2.17 pg/ml and 1,483+/-203 mosmol/kg in controls (NS). Water deprivation increased P(AVP) and U(osm) similarly in pregnant and virgin rats: these values reached 22.7+/-3.3 pg/ml and 3,300+/-123 mosmol/kg at 48 h in gravid compared with 26.0+/-6.4 pg/ml and 3,342+/-141 mosmol/kg in the controls (NS). Regression equations for P(AVP)vs. P(osm) which were highly significant (P < 0.001) in both groups demonstrated an apparent threshold for AVP secretion approximately 11 mosmol lower in gravid animals. Intravascular volume decreased, and plasma aldosterone increased during water deprivation, and both changes (Delta%) were significantly greater in the gravid animals (P <0.01). Therefore, P(osm) was increased without concomitant volume depletion by intraperitoneal hypertonic saline. Again P(AVP)vs. P(osm) correlated significantly (r > 0.9; P < 0.001) in each group, and the apparent threshold was 14 mosmol lower in pregnant animals. Diluting ability, tested by oral water loading, was not impaired in the pregnant animals which excreted a 30 ml/kg load as well as controls. Also, chronically hydrated virgin animals whose fluid intake was more than twice that of pregnant rats (for 19 d) did not lower their P(osm). In separate studies homozygous Brattleboro rats, which produce no endogenous vasopressin, were also shown to have a decreased P(osm) (pregnant 292+/-4 mosmol/kg; virgin 310+/-6 mosmol/kg P < 0.001), but unchanged U(osm) during pregnancy. Data demonstrate a resetting of the osmostat in gravid Sprague-Dawley rats as P(osm) and the threshold for AVP secretion both decrease significantly during gestation in this species. Studies in homozygous Brattleboro animals with hereditary diabetes insipidus suggest that the osmotic threshold for thirst is reset as well.
Assuntos
Arginina Vasopressina/metabolismo , Diabetes Insípido/complicações , Prenhez , Equilíbrio Hidroeletrolítico , Animais , Diabetes Insípido/fisiopatologia , Diurese , Comportamento de Ingestão de Líquido/fisiologia , Feminino , Capacidade de Concentração Renal , Concentração Osmolar , Gravidez , Ratos , Fatores de TempoRESUMO
The concept that acute increases in glomerular filtration rate (GFR) will cause large concomitant increases in sodium excretion has been re-examined. In previous work, GFR was elevated by volume expansion, usually with saline infusions. Recent evidence shows that tubular reabsorption is depressed during saline loading; hence, the independent effect of increased GFR on sodium excretion cannot be assessed.TO DETERMINE THE EFFECT OF ACUTE INCREASES IN GFR PER SE ON SODIUM EXCRETION, WE RAISED GFR BY FOUR TECHNIQUES NOT INVOLVING VOLUME EXPANSION: protein feeding, dopamine infusion, intravenous dexamethasone, and cross-circulation. GFR increased acutely by 5 to 85% in these experiments. In 12 of 24 experiments, GFR increased by more than 30%. In all but one experiment, sodium excretion increased by less than 75 muEq per minute. Data from experiments using each of the four techniques were comparable. The results were the same whether mineralocorticoid activity was high or low. In contrast, during saline loading, sodium excretion increased more than 800 muEq per minute with equal or lesser changes in GFR. These results demonstrate that acute increases in GFR per se have little effect on sodium excretion. We suggest that, due to constant fractional sodium reabsorption in the proximal tubule (glomerulotubular balance) and increased distal reabsorption, virtually all of the increase in filtered sodium is reabsorbed when GFR increases. Depression of tubular reabsorption is required for natriuresis.
Assuntos
Taxa de Filtração Glomerular , Sódio/urina , Absorção , Ácidos Aminoipúricos/urina , Animais , Transporte Biológico , Corticosterona/farmacologia , Dexametasona/urina , Cães , Dopamina/urina , Inulina/farmacologia , Túbulos Renais/metabolismo , Potássio/urina , Sódio/sangue , Espironolactona/farmacologia , Vasopressinas/farmacologiaRESUMO
The ability to excrete an oral water load and the renal diluting mechanism were studied in hypothyroid rats and in age-matched euthyroid controls. Hypothyroid animals excreted a significantly smaller fraction of a 50-ml/kg oral water load than controls, demonstrating the same limited ability to excrete free water as thyroid-deficient man. During hypotonic (0.45%) saline infusion, absolute sodium delivery to the diluting segment and free water clearance were markedly lower in hypothyroid rats. However, both fractional distal sodium delivery and fractional free water clearance were similar in hypothyroid and control animals, suggesting that the reduced absolute free water formation in hypothyroid rats was due to decreased net distal delivery. In support of this hypothesis was the observation that fractional distal sodium reabsorption was equal or higher in thyroid-deficient rats, which indicates that the sodium reabsorptive capacity of the diluting segment was preserved in these animals. The results cannot be attributed to incomplete suppression of antidiuretic hormone (ADH) since they were identical in diabetes insipidus rats, nor to different rates of non-ADH-dependent backflux of filtrate since tissue osmolality and solute concentrations in the cortex, medulla, and papilla were similar in hypothyroid and control rats of both Sprague-Dawley and Brattleboro strains. The functional integrity of the diluting segment in hypothyroid rats was further demonstrated in experiments in which distal delivery was increased by contralateral nephrectomy or by administration of carbonic anhydrase inhibitors which decrease proximal sodium reabsorption. In both studies, fractional free water clearance increased markedly reaching levels significantly greater than in euthyroid controls. These results demonstrate that the impaired ability of the hypothyroid rat to excrete a water load is not due to incomplete suppression of ADH or decreased reabsorptive capacity of the diluting segment but results from decreased filtrate delivery to this site secondary to reduced GFR.
Assuntos
Diurese , Hipotireoidismo/fisiopatologia , Animais , Inibidores da Anidrase Carbônica/farmacologia , Diurese/efeitos dos fármacos , Feminino , Taxa de Filtração Glomerular , Rim/fisiopatologia , Masculino , Concentração Osmolar , Ratos , Sódio/metabolismo , Urina , Equilíbrio HidroeletrolíticoRESUMO
Serial studies were designed to characterized changes in osmoregulation throughout gestation. Eight women underwent a 2-h infusion of hypertonic saline before conception, during gestational weeks 5-8, 10-12, and 28-33, and then 10-12 wk postpartum. Basal plasma osmolality (Posmol) was already significantly decreased by 5-8 wk (P less than 0.001) and remained 10 mosmol.kg-1 below nonpregnant values throughout pregnancy. The apparent threshold for AVP release (defined as the abscissal intercept of the regression line relating plasma AVP [PAVP] to Posmol) was also decreased significantly throughout gestation, as was the osmotic threshold for thirst (derived from analogue scales relating desire to drink to Posmol). The decrement in osmotic thirst threshold appeared to precede that for AVP release, and consistent with this 24-h urine volumes were significantly greater at 5-8 wk gestation (P less than 0.05). The slopes of each regression equation defining PAVP vs. Posmol (whose r values ranged from 0.79 to 0.99), very reproducible before and after pregnancy, were similar at 5-8 and 10-12 wk, but were markedly reduced in the third trimester (P less than 0.001). These volunteers had randomly undergone an additional infusion before conception (both tests in the luteal phase of the menstrual cycle) when 10,000 IU of human chorionic gonadotrophin (hCG) had been given intramuscularly over a 5-d period. Serum hCG values between 0.2 and 3.3 U.ml-1 were lower than usually seen in pregnancy, but the osmotic thresholds for AVP release and thirst decreased by 3 and 4 mosmol.kg-1, respectively (P less than 0.05). Finally we studied a patient with a molar pregnancy in whom thresholds for hormone release and thirst were both decreased to values resembling normal gestation and remained so for approximately 6 wk postevacuation, only normalizing when hCG had virtually disappeared from her serum. In contrast, thresholds increased within the first two puerperal weeks in two women with normal pregnancies. These data demonstrate (a) osmotic thresholds for both AVP release and thirst decrease within the very first gestational weeks; (b) increment in PAVP per unit increase in Posmol is reduced late in gestation; and (c) hCG may be involved in the osmoregulatory changes of pregnancy.
Assuntos
Arginina Vasopressina/metabolismo , Gonadotropina Coriônica/fisiologia , Idade Gestacional , Sede/fisiologia , Equilíbrio Hidroeletrolítico , Adolescente , Adulto , Líquidos Corporais/metabolismo , Feminino , Humanos , Mola Hidatiforme/fisiopatologia , Infusões Intravenosas , Gravidez , Solução Salina Hipertônica/administração & dosagem , Sede/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
To clarify alterations in carbohydrate metabolism which occur in pregnancy, metabolic clearance rates of insulin, proinsulin, and C-peptide were measured by the constant infusion technique in term-pregnant rats and in virgin littermates. In addition, placental permeability to these peptides was evaluated by simultaneous determination of their concentration in fetal blood, amniotic fluid, and maternal arterial blood and the renal extraction and excretion of insulin and C-peptide were determined during simultaneous studies of renal hemodynamics. The metabolic clearance rate (MCR) of insulin was higher (P less than 0.005) in pregnant animals (61.5+/-1.7 ml/min per kg nonconceptus body weight) than in virgin littermates (51.5+/-2.2 ml/min per kg). Insulin disappearance from the circulation after both single injection and discontinuance of a constant infusion was also faster in gravid animals. In contrast, the MCR of proinsulin and C-peptide, and the disappearance of C-peptide from the circulation were similar in pregnant and control rats. The placenta was virtually impermeable to each of the three polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally influenced by pharmacological concentrations as high as 60 ng/ml in the maternal circulation. The renal clearance of insulin (renal arteriovenous insulin difference X renal plasma flow) was lower, and its contribution to insulin MCR was less in pregnant animals than in controls (19.4+/-1.5% vs. 28.7+/-3.7%, P less than 0.05), whereas the renal clearance and renal clearance/MCR of C-peptide were similar in pregnant rats and virgin littermates. These results indicate that the peripheral metabolism of insulin is accelerated in pregnancy, while that of pro-insulin and C-peptide is unaffected. Since transplacental passage of insulin is negligible and its renal clearance is not increased, the enhanced MCR of insulin in pregnancy is due to increased metabolism at an extrarenal site probably within the placenta itself.
Assuntos
Insulina/metabolismo , Rim/metabolismo , Troca Materno-Fetal , Prenhez , Líquido Amniótico/química , Animais , Feminino , Sangue Fetal/química , Insulina/análise , Peptídeos/análise , Peptídeos/metabolismo , Gravidez , Proinsulina/análise , Proinsulina/metabolismo , RatosRESUMO
The vascular pathophysiology of preeclampsia, a hypertensive disorder unique to human pregnancy, has been postulated to be due to endothelial dysfunction, primarily manifest as deficient nitric oxide (NO) synthesis. We evaluated contraction (KCl and arginine vasopressin [AVP]) and dilation (acetylcholine and bradykinin) in small resistance-size omental arteries obtained during surgery from women with preeclampsia, postulating that these vessels would exhibit augmented contraction and diminished endothelium-dependent relaxation, most likely due to decreased NO synthesis. For comparison, vessels were also obtained from normotensive gravidas, pregnant women with chronic hypertension, or with chronic hypertension and superimposed preeclampsia, as well as from premenopausal nonpregnant controls. Vessels of approximately 200 micron in internal diameter were studied in vitro using a Mulvany-Halpern myograph. Maximal contraction due to either KCl or AVP was significantly augmented in vessels from women with preeclampsia; these vessels all exhibited endothelium- and cyclooxygenase-dependent phasic oscillations while vessels from all other groups exhibited only tonic contractions. Acetylcholine and bradykinin both led to dose- and endothelium-dependent relaxation which was unaffected by inhibitors of NO synthesis. Responses to bradykinin were similar in vessels from normal pregnant and preeclamptic women while those to acetylcholine were absent in vessels from women with preeclampsia. These data suggest specific defects in resistance-artery endothelium from women with preeclampsia.
Assuntos
Endotélio Vascular/fisiologia , Pré-Eclâmpsia/fisiopatologia , Vasodilatação , Acetilcolina/farmacologia , Adulto , Arginina Vasopressina/farmacologia , Artérias/fisiopatologia , Bradicinina/farmacologia , Feminino , Humanos , Óxido Nítrico/fisiologia , Nitroarginina/farmacologia , Omento/irrigação sanguínea , Gravidez , Vasodilatação/efeitos dos fármacosRESUMO
Metabolic clearance rates (MCR) of arginine vasopressin (AVP) were measured serially in five women starting before conception, during gestational weeks 7-8 (early), 22-24 (middle), and 36-38 (late pregnancy), and again 10-12 wk postpartum. Hormonal disposal rates were determined after water loading to suppress endogenous AVP release using a constant infusion method designed to achieve three different steady-state concentrations of plasma AVP (PAVP) on each test occasion. Dose schedules were altered in mid- and late pregnancy to obtain comparable AVP levels at each stage of the protocol. Prehydration decreased plasma osmolality sufficiently to suppress AVP release, as circulating AVP-neurophysin measured serially in three of the women was undetectable. The MCR of AVP was similar before conception (0.75 +/- 0.31, 0.79 +/- 0.34, and 0.76 +/- 0.28 liters/min at PAVP of 2.6 +/- 1.9, 4.7 +/- 2.4, and 8.3 +/- 3.9 pg/ml), in early pregnancy (0.89 +/- 0.34, 0.97 +/- 0.04, and 0.95 +/- 0.40 liters/min at PAVP of 2.2 +/- 2.1, 3.9 +/- 3.2, and 7.9 +/- 3.4 pg/ml), and postpartum (0.70 +/- 0.21, 0.69 +/- 0.24, and 0.75 +/- 0.20 liters/min at PAVP 3.5 +/- 1.8, 5.1 +/- 3.7, and 9.1 +/- 4.2 pg/ml). Values at mid-pregnancy (2.8 +/- 1.3, 3.0 +/- 1.2, and 2.7 +/- 1.2 liters/min at PAVP 2.3 +/- 2.2, 4.0 +/- 3.6, and 7.7 +/- 3.9 pg/ml) and late pregnancy (3.2 +/- 1.4, 3.3 +/- 1.4, and 2.9 +/- 1.2 liters/min at PAVP 1.9 +/- 2.0, 3.8 +/- 2.6, and 7.4 +/- 4.1 pg/ml) increased 3-4-fold (all P less than 0.01). Plasma vasopressinase, undetectable at 7-8 gestational wk, increased markedly by mid- and slightly more by late gestation. Finally, relationships between PAVP and urine osmolality were similar before, during, and after pregnancy. We conclude that marked increments in the MCR of AVP occur between gestational weeks 7 and 8 and mid-pregnancy, which parallel the period of greatest rise in both trophoblastic mass and plasma vasopressinase. There was no evidence of a renal resistance to AVP during gestation.
Assuntos
Aminopeptidases/sangue , Arginina Vasopressina/farmacocinética , Cistinil Aminopeptidase/sangue , Arginina Vasopressina/sangue , Feminino , Humanos , Infusões Intravenosas , Rim/fisiologia , Taxa de Depuração Metabólica , Neurofisinas/sangue , Período Pós-Parto/metabolismo , Gravidez , Gravidez MúltiplaRESUMO
Renal Na-K-ATPase activity changes adaptively in response to chronic alterations in sodium reabsorption or potassium secretion, but the role of this enzyme in rapid adjustments of renal tubular Na and K transport is not known. To evaluate this question, microsomal Na-K-ATPase specific activity and kinetics were determined in the rat and guinea pig kidney after massive but short-term (3 h) sodium or potassium loading. In other experiments renal sodium handling was evaluated in hydropenic and saline-loaded rats in which enzyme synthesis was prevented by the concurrent administration of actinomycin D or cycloheximide. Saline loading increased net sodium reabsorption in both rats and guinea pigs, but microsomal Na-K-ATPase from the outer medulla (where the reabsorptive increment is greatest) did not change significantly in either species. In vitro [3H]ouabain bidint to guinea pig microsomes and apparent Km for sodium of rat microsomal Na-K-ATPase, both from outer medulla, were also unaltered. Actinomycin D and cycloheximide failed to increase sodium excretion and microsomal Na-K-ATPase remained unchanged. KCL loading resulted in a 10-fold increase in K excretion but again Na-K-ATPase specific activity (in cortex, outer medulla, and papilla), and its apparent Km for potassium were not affected. Taken together these results suggest that rapid adjustments in remal tubular Na or K transport are mediated by mechanisms that do not involve the Na-K-ATPase enzyme system.
Assuntos
Adenosina Trifosfatases/metabolismo , Túbulos Renais/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Animais , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Taxa de Filtração Glomerular , Cobaias , Córtex Renal/enzimologia , Medula Renal/enzimologia , Masculino , Microssomos/efeitos dos fármacos , Microssomos/enzimologia , Ouabaína/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Cloreto de Sódio/farmacologiaRESUMO
The cause of oral-contraceptive-induced hypertension in certain susceptible subjects is obscure. We describe a woman who was receiving replacement doses of fludrocortisone acetate after adrenalectomy and hypophysectomy who developed high blood pressure while ingesting an estrogen-containing oral contraceptive. Renin substrate level was increased, but renin activity was suppressed and unresponsive to tilting. The patient developed a markedly exaggerated natriuresis when infused with saline. Both blood pressure and her responses to infused sodium and tilting normalized after discontinuance of the oral contraceptive medication. In this adrenalectomized patient, the estrogenic component of the pill acting synergistically with a fixed ("nonsuppressible") replacement dose of mineralocorticoid seems to have caused a volume-related hypertension.
Assuntos
Adrenalectomia , Hipertensão/induzido quimicamente , Hipofisectomia , Mestranol/efeitos adversos , Noretindrona/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Adenoma Cromófobo/cirurgia , Adulto , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hipertensão/metabolismo , Rim/metabolismo , Testes de Função Renal , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/metabolismo , Sódio/metabolismoRESUMO
High blood pressure, which complicates approximately 10% of all pregnancies, remains a major cause of morbidity and mortality for both mother and fetus. A relative paucity of investigative data, as well as the frequent difficulty in making an etiological diagnosis by clinical criteria alone, may be among the reasons why there are many conflicts about the management of hypertension during pregnancy. This clinical conference summarizes current concepts regarding the hypertensive disorders of gestation, focusing on the most dangerous cause, preeclampsia-eclampsia. It further highlights a recent report of the Working Group on High Blood Pressure in Pregnancy convened by the National High Blood Pressure Education Program at the National Heart, Lung, and Blood Institute (the Consensus Report). Among the Working Group's most interesting recommendations in controversial areas were a return to the classification schema suggested by the American College of Obstetricians and Gynecologists in 1972, use of the fifth Korotkoff sound to determine diastolic blood pressure levels, and institution of treatment with antihypertensive drugs for sudden elevations of blood pressure near term to diastolic levels greater than or equal to 105 mm Hg or for levels of 100 mm Hg or higher in pregnant women with chronic hypertension. The Consensus Report further recommended parenteral hydralazine and methyldopa as the drugs of choice for the acute hypertensive crisis and management of chronic hypertension, respectively, based on the long histories of safe use of these agents in gravidas. Parenteral magnesium sulfate remained the preferred therapeutic approach for avoiding or treating the convulsive complication, eclampsia, but the Working Group underscored the need for controlled trials of magnesium's efficacy. Finally, they noted that diuretics should be avoided in preeclampsia, but that these drugs can be continued during gestation if taken before conception, and may be prescribed to pregnant women with chronic hypertension who appear overly salt sensitive.
Assuntos
Eclampsia , Hipertensão , Pré-Eclâmpsia , Complicações Cardiovasculares na Gravidez , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Eclampsia/fisiopatologia , Eclampsia/prevenção & controle , Feminino , Humanos , Hipertensão/tratamento farmacológico , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/prevenção & controle , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/prevenção & controleRESUMO
This study was designed to determine the roles of the sympathetic nervous system, adrenal medulla, and arginine vasopressin (AVP) in mediating pressor and plasma activity (PRA) responses to intraventricularly (ICV) administered prostaglandin E2 (PGE2) in conscious rats. The ICV PGE2 elevated blood pressure and caused increases in PRA, plasma AVP, and plasma norepinephrine and epinephrine. The pressor effect of ICV PGE2 was not influenced by pretreatment with captopril, but was attenuated by the AVP antagonist, d(CH2)5Tyr(Me)AVP, and by phenoxybenzamine, and was completely abolished by the combination of the AVP antagonist and phenoxybenzamine. The PRA response to ICV PGE2 was not affected by bilateral renal denervation or by phenoxybenzamine alone, but was attenuated by propranolol alone and was completely abolished by the combination of propranolol and phenoxybenzamine. Bilateral adrenomedullectomy did not affect the pressor response to ICV PGE2, whereas it attenuated the increase in PRA and completely abolished the increase in plasma epinephrine. These results suggest that the pressor effect of ICV PGE2 is the result of increased sympathetic nervous system activity and is dependent on the stimulation of alpha-adrenergic receptors and on AVP release. The pressor response to ICV PGE2 is accompanied by but not dependent on an increase in PRA. The renin-stimulating effect of centrally administered PGE2 is, at least in part, dependent on beta-adrenergic receptor stimulation by increased circulating catecholamines.
Assuntos
Arginina Vasopressina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Prostaglandinas E/farmacologia , Renina/sangue , Medula Suprarrenal/fisiologia , Inibidores da Enzima Conversora de Angiotensina , Animais , Arginina Vasopressina/antagonistas & inibidores , Captopril/farmacologia , Denervação , Dinoprostona , Inibidores Enzimáticos , Injeções Intraventriculares , Rim/inervação , Masculino , Fenoxibenzamina/farmacologia , Prostaglandinas E/administração & dosagem , Ratos , Ratos Endogâmicos , Sistema Nervoso Simpático/fisiologiaRESUMO
Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 micrograms/0.5 microliter/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 +/- 3.3 compared to 181 +/- 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICV-injected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p less than 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control.
Assuntos
Captopril/administração & dosagem , Prolina/análogos & derivados , Inibidores da Enzima Conversora de Angiotensina , Animais , Arginina Vasopressina/análise , Arginina Vasopressina/sangue , Encéfalo/enzimologia , Química Encefálica , Captopril/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Desidratação/fisiopatologia , Injeções Intraventriculares , Masculino , Nervos Periféricos/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Sistema Renina-Angiotensina , Sódio/metabolismoRESUMO
Effects of gestation on volume homeostasis and renal function were studied in awake spontaneously hypertensive rats (SHR). Systolic blood pressure was similar to that of virgin littermates during most of SHR pregnancy but decreased near term (p less than 0.005). Plasma renin activity was lower in SHR than in age-matched Wistar-Kyoto (WKY) rats (p less than 0.001), but values were similar in gravid and nonpregnant animals from each strain. Renal renin content and lipid volume fractions of papillary interstitial granules were significantly greater in pregnant animal of each strain and those of the gravid WKY were also greater than both pregnant and virgin SHR. Saralasin had no effect on mean arterial pressure in gravid and virgin rats from either group. Plasma volume increased significantly near term in animals of both strains. Kidney weight, glomerular filtration rate (GFR), and renal blood flow were lower in SHR compared to WKY, and the hypertensive rats failed to demonstrate an increase in GFR during gestation, unlike the WKY. All SHR and pregnant WKY excreted infused sodium better than the virgin WKY. Also, regular Wistar animals excreted a salt load better than the virgin WKY. Finally, uterine blood flow, pup number and conceptus weight were similar in SHR and WKY. We conclude that pregnancy induces a decrease in blood pressure in SHR, and that angiotensin II does not seem to play an important role in maintaining blood pressure during gestation in either SHR or WKY. Despite a lower GFR and its failure to increase during pregnancy, renal sodium handling is not impaired in the SHR. The virgin WKY has a decreased ability to excrete sodium which is ameliorated during gestation.
Assuntos
Pressão Sanguínea , Hipertensão/fisiopatologia , Rim/fisiopatologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Animais , Feminino , Taxa de Filtração Glomerular , Hemodinâmica , Medula Renal/patologia , Metabolismo dos Lipídeos , Natriurese , Volume Plasmático , Gravidez , Ratos , Ratos Endogâmicos , Sistema Renina-AngiotensinaRESUMO
A 30-year-old woman with a living related six-antigen-matched kidney allograft conceived 10 years posttransplantation. She had discontinued her immunosuppression medications 3 years previously. The allograft functioned well throughout gestation, which was complicated by preeclampsia, leading to induction at 35 weeks and delivery of a 2,175-g male.