Plasma Volume Contraction: A Significant Factor in Both Pregnancy-Associated Hypertension (Pre Eclampsia) and Chronic Hypertension in Pregnancy

The role of plasma volume in hypertension in pregnancy (pre-eclampsla)was investigated. Significant volume expansion from non-pregnantlevels (16·5 ± 1·60 ml/cm height) was presentthroughout pregnancy in 189 normal women, reaching 23·1± 1·21 ml/cm at 33–36 weeks amenorrhoea.In another 40 initially normotensive pregnant women who developedhypertension, simllar early volume expansion was followed bysignificant volume contraction in the third trimester, beforeelevation of blood pressure in 29 (20·6 ± 1·26ml/cm), after it in 11(18·6 ± 1·27 ml/cm).Equivalent volume contraction was present in another 44 womenstudied only after hypertension developed in the third tri mester.Oedema had no value as a clinical sign. In another 30 women with chronic hypertension, blood pressurewas inversely related to plasma volume (r = –0·822)and to fetal growth (r = –0·710), which was directlyrelated to plasma volume (r=0·701). Plasma volume depletionplays a significant role in hypertension in pregnancy.     

The influence of pregnancy on drug action: concentration-effect modelling with propranolol

The physiological changes of pregnancy have been shown to alter the disposition of some drugs. However, there are no data on the possible influence of pregnancy or its complications on drug effect. We have applied drug concentration-effect analysis to determine whether pregnancy influences the action of propranolol. Twelve women with pregnancy induced hypertension were studied during the third trimester and again 2-3 months post partum. On each occasion propranolol (10 mg) was given intravenously and measurements of heart rate, blood pressure and whole blood propranolol concentration were determined over the ensuing 8 h. Pregnancy did not alter propranolol disposition. Clearance was 0.63 +/- 0.18 and 0.71 +/- 0.24 litre h-1 kg-1, and volume of distribution at steady state was 4.02 +/- 2.98 and 3.07 +/- 1.58 litres/kg during and after pregnancy respectively. There was no fall in blood pressure over the period of the acute study. The reduction in heart rate (beats/min per ng of propranolol/ml) was greater during compared with after pregnancy: -0.61 +/- 0.23 and -0.39 +/- 0.19 respectively (F = 6.64; df 1.9; P less than 0.03). There was no relationship between blood pressure or pretreatment heart rate and the slope of the concentration-effect relationship. We conclude that pregnancy can significantly alter drug effect in the absence of any pharmacokinetic changes. These findings suggest that therapeutic ranges established in non-pregnant patients may not be applicable during pregnancy.     

Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means+/-S.E.M. plasma VEGF(165)b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF(165)b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90+/-1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40+/-0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF(165)b levels were lower than in the normotensive group (0.467+/-0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF(165)b concentrations were greater than normal in both pre-eclamptic (3.75+/-2.24 ng/ml) and normotensive (10.58 ng/ml+/-3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF(165)b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20+/-0.07 and 1.27+/-0.18 ng/ml) and sEng (4.4+/-0.18 and 4.1+/-0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF(165)b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF(165)b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.     

Plasma catecholamines in pregnancy induced hypertension

Increased activity of the sympathetic nervous system has been implicated in the genesis of early hypertension in young people. Studies in pregnancy allow observations to be made on evolving, recently established and resolving hypertension in the human. We describe the results of two studies involving women who developed hypertension during pregnancy. In the first study, plasma concentrations of noradrenaline and adrenaline were measured in 17 women with pregnancy induced hypertension (PIH) and 17 normotensive pregnant control subjects. Plasma noradrenaline (nmol/l) was lower in the PIH group compared with control patients in both semi-recumbent (1.11 +/- 0.53 vs 1.98 +/- 0.96, P less than 0.001) and standing positions (1.31 +/- 0.65 vs 2.57 +/- 1.27, P less than 0.005). Five days post partum, plasma noradrenaline had risen in the PIH group compared with pregnant values in semi-recumbent (1.65 +/- 1.0 vs 1.11 +/- 0.52, P less than 0.05) and standing positions (2.46 +/- 1.5 vs 1.31 +/- 0.65, P less than 0.05). In the normotensive patients plasma noradrenaline did not differ between post partum and pregnant values (1.51 +/- 0.73 vs 1.98 +/- 0.96 semi-recumbent; 2.00 +/- 1.16 vs 2.57 +/- 1.7 standing). Logarithmic transformation of the noradrenaline concentration data resulted in a significant (P less than 0.02) negative correlation with diastolic blood pressure in the pregnant patients but not post partum. Plasma adrenaline concentration was the same in both groups. In the second study, plasma concentrations of noradrenaline and adrenaline were measured sequentially through pregnancy in five women who developed PIH and five control subjects who remained normotensive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma levels of atrial natriuretic peptide in patients with borderline and essential hypertension

Plasma levels of atrial natriuretic peptide (ANP) were measured in outpatients with borderline hypertension (n = 15) and essential hypertension (n = 13) and in normotensive subject (n = 11). There were no significant differences among the three groups in age, serum protein, albumin, or electrolyte levels, plasma renin activity (PRA), or plasma concentrations of aldosterone and cortisol. The plasma ANP levels in the normotensive, borderline hypertensive, and essential hypertensive subjects were 36 +/- 6 pg/ml (mean +/- S.E.), 64 +/- 11 pg/ml, and 82 +/- 14 pg/ml, respectively. The levels in the essential hypertensive subjects were significantly (p less than 0.05) higher than those in the normotensives. In both borderline and essential hypertensives (n = 28), the plasma ANP levels were significantly correlated positively with systolic blood pressure (r = +0.385, p less than 0.05), and negatively with PRA (r = -0.484, p less than 0.05) and serum total calcium (r = -0.516, p less than 0.01). These results suggest that the elevation of circulating ANP in hypertensives is involved in the pathogenesis of hypertension.     

Maternal and fetal atrial natriuretic peptide levels, maternal plasma renin activity, angiotensin II, prostacyclin and thromboxane A2 levels in normal and preeclamptic pregnancies.

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.     

Characterization of subtypes of hypertension in CAPD patients by cyclic guanosine monophosphate.

OBJECTIVE: While most hypertensive patients with end-stage renal disease normalize high blood pressure with fluid removal by continuous ambulatory peritoneal dialysis (CAPD), there is a significant proportion of CAPD patients whose blood pressure can be controlled only by antihypertensive drugs. METHOD AND PATIENTS: To study the hypothesis that such patients are still volume overloaded, we used plasma cyclic guanosine monophosphate (cGMP) as a marker for hydration status. Thirty-two CAPD patients were divided into 3 groups: group 1, normotensive patients (n = 12); group 2, hypertensive patients who normalized their blood pressure with fluid removal (n = 12); group 3, hypertensive patients whose blood pressure was refractory to intensified fluid removal (n = 8). RESULTS: Mean cGMP levels were significantly higher in dialysis-sensitive hypertension (27 +/- 5 pmol/mL) than in dialysis-refractory hypertension (15 +/- 2 pmol/mL), or in normotensive patients (13 +/- 4 pmol/mL). Reduction of excess fluid in volume overloaded hypertensive CAPD patients resulted in a normalization of cGMP levels (14 +/- 8 pmol/mL), but did not affect this volume marker in patients with dialysis-resistant hypertension (10 +/- 4 pmol/mL). CONCLUSION: Plasma cGMP levels are elevated in volume overload-induced hypertension complicating CAPD. Hypertensive CAPD patients whose plasma cGMP levels are within normal limits have raised blood pressure refractory to volume removal. Our findings are consistent with the hypothesis that inadequate removal of excess volume plays a major role in a subset of patients with CAPD hypertension.     

Cardiovascular effects of verapamil in essential hypertension

Calcium antagonists may affect the regulation of body sodium and adrenergic-dependent mechanisms. Exchangeable sodium, blood volume, plasma norepinephrine, renin, aldosterone, pressor responsiveness to norepinephrine, heart rate responses to isoproterenol, and lipid metabolism were studied in 15 patients with essential hypertension after 8 weeks of treatment with verapamil (348 +/- 68 (SD) mg/day). Supine blood pressure decreased from 153/103 +/- 19/12 mm Hg to 140/95 +/- 14/12 mm Hg (P less than 0.01). Exchangeable sodium, blood volume, plasma norepinephrine, renin and aldosterone, serum total cholesterol, the lipoprotein fractions, and apoprotein levels were unchanged. The norepinephrine pressor and the isoproterenol chronotropic doses tended to increase, whereas the dose-response curve of blood pressure related to plasma norepinephrine was significantly displaced to the right (F = 5.34; P less than 0.05). The antihypertensive effect of verapamil is associated with a decreased cardiovascular pressor responsiveness to norepinephrine without changes in endogenous noradrenergic activity. Moreover, verapamil does not modify the sodium/fluid volume state, the activity of the renin-angiotensin aldosterone axis, or lipid metabolism.     

Effect of acute vascular fluid volume expansion on erythrocyte sodium transport in essential hypertension

Evidence exists that volume expansion is associated with the appearance of a circulating sodium transport inhibitor. We have evaluated intra-arterial blood pressure (BP), central venous pressure (CVP), plasma renin activity (PRA), intraerythrocyte sodium content, erythrocyte sodium influx and rate constant of sodium efflux in 10 untreated primary hypertensive men (WHO stages I and II). The investigations were done during baseline conditions and after rapid intravenous infusion of 1 litre of saline (0.9% NaCl solution) over 15-20 min. Volume expansion caused an increase in CVP by 6.0 +/- 0.5 cmH2O (p less than 0.01), while BP only exhibited a slight increase. No significant changes in intraerythrocyte sodium content, sodium influx, sodium efflux rate constant or PRA were found after volume expansion compared to baseline. All patients with low normal PRA experienced a decrease in sodium efflux rate constant after volume expansion. We found a positive correlation between baseline PRA and change in sodium efflux rate constant after volume expansion (r = 0.62, p less than 0.05). At baseline the relationship between PRA and intraerythrocyte sodium content nearly reached statistical significance (r = 0.63, p = 0.054). These results may indicate that acute volume expansion influences the release of a circulating factor, modulating sodium transport in low-renin hypertension.     

Hyperhomocysteinemia is related to a decreased blood level of vitamin B12 in the second and third trimester of normal pregnancy.

Hyperhomocysteinemia has been associated with several pregnancy complications. We have investigated the variation of plasma total homocysteine (tHcys) during the 2 last trimesters of normal pregnancy and related it to blood vitamin B12 and folate and to the excretion of the degraded intrinsic factor receptor (IFCR) in urine, in a follow-up study of 15 cases. A significant rise in tHcys was observed between the beginning of the second trimester and the third trimester with respective values (median) 6.1, 5.8 and 6.7 micromol/l (p = 0.038). The tHcys/albumin ratio also increased significantly, while no correlation was found between albumin and folate blood concentration. In contrast, a significant decrease in vitamin B12 was observed (279, 225 and 199 pmol/l, between the 4th and 6th, and the 6th and 9th month, respectively (p = 0.017-0.002)). A significant negative correlation was found between tHcys between the 4th and 9th month of pregnancy and the ratio of vitamin B12 between the 4th and 9th month of pregnancy (r = 0.55, p = 0.037). The urine excretion of IFCR was increased and was not related to vitamin B12 and tHcys. In conclusion, we have observed a rise in tHcys between the beginning of the second trimester and the third trimester of pregnancy which was related to the decreased blood level of vitamin B12. Subclinical deficiency of vitamin B12 should be further investigated in pregnant women who remain on inadequate diet.     

Capillary hypertension and abnormal pressure dynamics in patients with essential hypertension

1. Pressure was measured within 28 capillaries of the nailfolds of nine patients with essential hypertension and in 33 capillaries of nine age- and sex-matched normotensive control subjects, using direct micropuncture, a dynamic servo-nulling system and computerized analysis. 2. Average pressure at the apex of the capillary was found to be elevated in the patients with hypertension (21.1 +/- 4.9 mmHg compared with 13.0 +/- 2.0 mmHg in the control subjects; mean +/- SD, P less than 0.01). If the two groups were combined, there was an overall correlation between average capillary pressure and mean blood pressure (r = 0.68, P less than 0.01, n = 18), but within each group separately there was no significant relation between these parameters. 3. There were also abnormalities in the waveforms of pulsations in capillary pressure in the group with hypertension, with an increased attenuation of high-frequency harmonics. Pulses appeared to be conducted more rapidly along the vascular tree in the patients with hypertension. 4. The elevation of capillary pressure in essential hypertension demonstrated in this study is in agreement with indirect evidence of capillary hyperfiltration provided by other studies which showed a reduced plasma volume and increased transcapillary escape rate of plasma proteins. 5. The finding of elevated capillary pressure demands the inclusion of the postcapillary segment (and possibly vascular density) in the resistance equation in essential hypertension.     

The renin-angiotensin-aldosterone system and arterial hypertension in patients with rheumatoid arthritis

Renin-angiotensin-aldosterone++ system was investigated in 60 patients suffering from rheumatoid arthritis. Forty-four of them (group 1) had arterial hypertension (144 +/- 4/94 +/- 2 mm Hg), sixteen were free of hypertension (120 +/- 3/80 +/- 1 mm Hg). Twenty-nine control subjects comparable by AH standing and demographic parameters had essential hypertension stage IB-IIA by A. L. Myasnikov classification (141 +/- 3/89 +/- 1 mm Hg). A tendency to renin suppression was dominating in 72% of group 1 patients (plasma renin activity less than 1.0 ng/ml/h). In this group there appeared high concentrations of A II (14.2 +/- 3.1 pg/ml) and plasma aldosterone++ (238 +/- 94 ng/ml). Rheumatoid vasculitis manifested in 86% of patients. Control subjects exhibited plasma renin activity greater than 3.0 ng/ml/hin 48%, average A II concentration was similar to that of group 1 (12.4 +/- 2.7 ng/ml/h, p greater than 0.05), plasma aldosterone++ level was significantly lower (176 +/- 29 ng/ml, p less than 0.05). Correlations were established between A II concentration and ESR (r = 0.39, p less than 0.05), A II and rheumatoid factor titers (r = 0.40, p less than 0.05). These indicate that immunopathological reactions are responsible for shifts in renin-angiotensin-aldosteron system in hypertensive rheumatoid arthritis subjects.     

Theophylline pharmacokinetics in pregnancy

Theophylline pharmacokinetics were studied serially in five women during and after pregnancy. Theophylline protein binding was reduced to 11.1% +/- 4.7% (P less than 0.01) and 13.0% +/- 5.9% (P less than 0.01) during the second and third trimesters of pregnancy, respectively, compared with 28.1% +/- 2.8% when the patients were more than 6 months postpartum. Similar comparisons indicate that theophylline distribution volume and elimination t1/2 were increased from 30.7 +/- 4.4 L and 262 +/- 57 minutes to 36.8 +/- 4.2 L (P less than 0.05) and 389 +/- 73 minutes (P less than 0.01) in the third trimester of pregnancy. In the second and third trimesters, intrinsic nonrenal clearance was reduced to 0.82 +/- 0.25 ml/min X kg (P less than 0.05) and 0.67 +/- 0.18 ml/min X kg (P less than 0.01) compared with a remote postpartum value of 1.25 +/- 0.37 ml/min X kg. However, these reductions were offset by increases in theophylline intrinsic renal clearance so that apparent reductions in the overall unbound clearance of this drug did not reach statistical significance either during pregnancy or in the early postpartum period.     

A cross-sectional study of basal platelet intracellular free calcium concentration in normotensive and hypertensive primigravid pregnancies

1. The intracellular free calcium concentration ([Ca2+]i) in washed human platelets was measured using the fluorescent indicator, fura-2, in a cross-sectional study of 36 normotensive, primigravid volunteers, 12 in each trimester of pregnancy and a further 12 at 6 weeks post partum. The results were compared with those obtained from 30 normal female volunteers not using oral contraception. 2. The mean basal [Ca2+]i in the platelets of the pregnant women in the first two trimesters (115.6 +/- 6.7 and 120.1 +/- 5.7 nmol/l, respectively) was not shown to differ significantly from that of normal non-pregnant volunteers (112.3 +/- 2.9 nmol/l). However, during the third trimester a significant increase in [Ca2+]i was noted (134.0 +/- 4.9 nmol/l; P less than 0.05), with a return to normal values in the post-partum period (108.2 +/- 6.1 nmol/l). 3. [Ca2+]i was also measured in the platelets of a group of 12 primigravid pregnant women in the third trimester whose pregnancies were complicated by gestational hypertension (pregnancy-induced hypertension and pre-eclampsia). A significant rise in basal [Ca2+]i was noted in the platelets of primigravidae whose pregnancies were complicated by pre-eclampsia (163.6 +/- 8.8 nmol/l) as compared with normotensive, third-trimester primigravidae (P less than 0.02). However, no correlation could be demonstrated between [Ca2+]i and systemic blood pressure.     

Calcium and magnesium in essential hypertension

1. Because disturbances of calcium metabolism have been described in hypertension, measurements of plasma and serum concentrations of ionized calcium, total calcium, magnesium and renin were made in 38 patients with essential hypertension and age- and sex-matched control subjects. Urinary excretion of calcium, magnesium and sodium was also determined. 2. The mean serum concentration of ionized calcium was 1.23 +/- 0.04 (SD) mmol/l in the hypertensive group and 1.21 +/- 0.03 mmol/l in controls, and results were similar after correction for pH. There was a weak positive correlation between serum ionized calcium (pH 7.4) and systolic pressure (r = 0.26, P less than 0.02), but no correlation with plasma renin concentration. 3. Although the difference between serum total calcium concentration in the hypertensive (2.29 +/- 0.09 mmol/l) and control (2.26 +/- 0.07 mmol/l) subjects was not significant, there was a significant correlation between total calcium and systolic pressure (r = 0.23, P less than 0.05) which was maintained after correction for other variables. 4. There were no differences in plasma concentrations of parathyroid hormone or 1,25-dihydroxycholecalciferol between hypertensive and control subjects. 5. The hypertensive group showed higher urinary excretion of calcium (5.9 +/- 3.0 mmol/24 h) than controls (4.6 +/- 1.7 mmol/24 h), but the difference was not maintained after correction for sodium excretion. 6. Serum concentrations of magnesium were similar in the two groups, but urinary excretion of magnesium was significantly lower in hypertensive (3.7 +/- 1.3 mmol/24 h) than control (4.5 +/- 1.6 mmol/24 h) subjects and there was an inverse correlation between magnesium excretion and blood pressure (r = 0.3-0.35, P less than 0.01).     

Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension.

The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA.     

妊娠晚期孕妇心理弹性与焦虑的相关性研究

目的：调查妊娠晚期孕妇心理弹性及焦虑状况,探讨妊娠晚期孕妇心理弹性与焦虑的相关性。方法：采用心理弹性量表（CD-RISC）和焦虑自评量表（SAS）对253例妊娠晚期孕妇进行问卷调查。结果：妊娠晚期孕妇的心理弹性得分为38~94（65.21±11.08）分,坚韧、力量、乐观维度得分分别为16~52（31.40±6.93）分、13~32（22.99±3.80）分、5~16（10.83±2.01）分。妊娠晚期孕妇的焦虑得分为26~70（44.64±8.91）分,46（18.2％）例孕妇处于轻度焦虑,15（5.9％）例孕妇处于中度焦虑,2（0.8％）例孕妇处于重度焦虑。妊娠晚期孕妇的心理弹性和焦虑程度呈负相关（r=-0.573,P<0.001）,坚韧维度和焦虑程度呈负相关（r=-0.491,P<0.001）,力量维度和焦虑程度呈负相关（r=-0.365,P<0.001）,乐观维度和焦虑程度无相关关系（r=-0.164,P=0.09）。妊娠晚期孕妇的焦虑程度与心理弹性、妊娠期合并症及并发症、不良孕产史有线性回归关系。结论：孕妇的心理弹性能够影响妊娠晚期的焦虑程度,可从提高孕妇心理弹性水平的角度改善妊娠晚期孕妇的心理健康状况。     

Usefulness of ambulatory blood pressure monitoring in pregnant women with type 1 diabetes.

OBJECTIVE: Pregnancy in type 1 diabetes is associated with an increased risk of developing pregnancy-induced hypertension (PIH). Ambulatory blood pressure monitoring (ABPM) has been used to screen for preeclampsia in nondiabetic pregnancy. To date, there are no data regarding ABPM during pregnancy in normotensive type 1 diabetic women. This study sought to establish blood pressure (BP) profiles for pregnant type 1 diabetic women using ABPM and determine whether the BP pattern can define a population at risk for developing PIH. RESEARCH DESIGN AND METHODS: ABPM was carried out for one 24-h period during each trimester--in the first trimester between weeks 7 and 12, in the second trimester between weeks 20 and 24, and in the third trimester between weeks 30 and 34--in 22 normotensive pregnant type 1 diabetic and 10 pregnant nondiabetic women. RESULTS: The incidence of PIH was fourfold greater in type 1 diabetic women than in control subjects. Diabetic women showed higher daily diastolic BP in the third trimester compared with nondiabetic pregnant women. Diabetic women who developed PIH in the third trimester showed significantly higher BP profiles throughout gestation than those who remained normotensive. Receiver operator characteristics curves for nighttime systolic BP showed the best predictive capacity for PIH, with a cutoff > 105 mmHg (85% sensitivity and 92% specificity). CONCLUSIONS: Our study confirms the early increase of BP in patients who will develop PIH and suggests that nighttime systolic BP >105 mmHg in the second trimester is a useful predictor of PIH. ABPM may be useful in screening for PIH in pregnant diabetic women.     

Characterization of theophylline binding to serum proteins in pregnant and nonpregnant women

Sera from 10 subjects in the third trimester of pregnancy and from 10 nonpregnant women were studied to elucidate the mechanism underlying decreased theophylline protein binding during pregnancy. Consistent with the physiologic hypoalbuminemia of pregnancy, serum albumin concentrations averaged only 3.2 +/- 0.3 gm/dl (+/- SD) in pregnant subjects, compared with 4.4 +/- 0.3 gm/dl in control subjects (p less than 1 x 10(-6], and this was the main cause of decreased theophylline binding. Saturation binding studies indicated a single class of theophylline binding sites. Theophylline binding capacity (N) was greater in pregnant (N = 4.3 +/- 1.0) than in nonpregnant (N = 3.3 +/- 0.4) subjects, but binding affinity (ka) averaged only 227 +/- 69 (mol/L)-1 in pregnant subjects, compared with 303 +/- 44 (mol/L)-1 in control subjects (F2,17 = 4.26; p = 0.032). At a theophylline plasma concentration of 10 micrograms/ml, the combined effects of hypoalbuminemia and lowered ka would reduce theophylline binding to 31% +/- 3% in pregnant women, compared to 39% +/- 3% in nonpregnant control subjects (p less than 1 x 10(-5]. Nonesterified fatty acid concentrations were similar in both subject groups and did not contribute to the pregnancy-associated decrease in theophylline binding.     

Atrial natriuretic peptide in human essential hypertension

We measured the circulating levels of atrial natriuretic peptide (ANP) in 62 patients with untreated uncomplicated essential hypertension and in 30 normotensive subjects. In the hypertensive patients, mean systolic and diastolic blood pressures were 148 and 101 mm Hg, respectively, and the mean heart rate was 73 beats/min. ANP concentrations were not elevated in the hypertensive group but were actually decreased slightly over those of the control group (27.4 +/- 1.8 pg/ml versus 35.3 +/- 2.4 pg/ml [P less than 0.02]). No relationship was found between ANP levels and diastolic blood pressure, plasma renin activity, urinary sodium excretion, or serum creatinine level. In 8 of the 62 patients with essential hypertension, 6 weeks of treatment with a dihydropyridine calcium channel blocker, nitrendipine, significantly reduced plasma ANP levels from 28.6 +/- 4.3 pg/ml to 18.7 +/- 1.8 pg/ml (P less than 0.05). In 17 additional patients treated with the hypotensive agent ketanserin, ANP levels were not significantly reduced after treatment. Thus, this study demonstrates that circulating plasma ANP levels are not increased but are slightly decreased in patients with uncomplicated essential hypertension in comparison with normotensive subjects. Furthermore, antihypertensive treatment with a calcium channel antagonist reduced plasma levels of ANP.