A multicenter prospective study of home blood pressure measurement (HBPM) during pregnancy in Japanese women.

In the near future, hypertensive disorders of pregnancy (HDP) have been diagnosed by home blood pressure monitoring (HBPM) instead of clinic BP monitoring. A multicenter study of HBPM was performed in pregnant Japanese women in the non-high risk group for HDP. Participants were women (n = 218), uncomplicated pregnancy who self-measured and recorded their HBP daily. Twelve women developed HDP. HBP was appropriate (100 mmHg in systole and 63 mmHg in diastole), bottoming out at 17 to 21 weeks of gestation. It increased after 24 weeks of gestation and returned to non-pregnant levels by 4 weeks of postpartum. The upper limit of normal HBP was defined as the mean value +3 SD for systolic and mean +2 SD for diastolic with reference to the criteria for non-pregnant women. Using the polynomial equation, the hypertensive cut-off of systolic HBP was 125 mmHg at 15 weeks and 132 mmHg at 30 weeks of gestation, while it for diastolic HBP was 79 mmHg at 15 weeks and 81 mmHg at 30 weeks of gestation. Systolic HBP in women who developed HDP was higher after 24 weeks of gestation, and diastolic HBP was higher during most of the pregnancy compared to normal pregnancy. When the variability of individual HBP in women developed HDP compared to normal pregnant women was examined using the coefficient of variation (CV), the CV was lower in HDP before the onset of HDP. HBPM can be used not only for HDP determination, but also for early detection of HDP.

[Management of pregnancy induced hypertension].

Pregnancy induced hypertension (PIH) is classified according to the severity of hypertension. The Japan Society of Hypertension made practice guidelines in 2014, and the Japan Society for the Study of Hypertension in Pregnancy made guidelines subsequently in 2015, too. Both guidelines state that the basic treatment for PIH is the interruption of pregnancy, and antihypertensive therapy should be given for protection in mother complicated by severe hypertension. The fetal heart rates should be monitored enough due to worsening fetal circulation. It recommends that methyldopa, hydralazine, labetalol, and long-acting nifedipine (only after 20 weeks of gestation) should be used as the first-choice antihypertensive oral drugs. Intravenous administration should be selected when a hypertensive emergency occurs.

PP041. The underlying mechanisms in reduced action of endothelial nitric oxide in resistance artery in preeclampsia.

OBJECTIVE: In preeclampsia (PE), the action of endothelial nitric oxide (eNO) is reduced by in vitro investigation of characteristic changes using vascular strips of resistance artery. We studied underlying mechanisms in the reduced action of it. METHODS: The vascular strips of omental resistance arteries were obtained from PE and normotensive pregnant women. Informed consent was obtained from each patient. This study was permitted by ethical board. (1) The various isometric tension by NO were measured by bradykinin (BK), sodium nitroprusside (SNP) and the inhibition of 8-pCPT-cGMPVert@during the STA2 (a stable analogue of thromboxane A2)-induced contraction. (2) The [Ca(2+)]i were measured in the endothelium-intact strip loaded cell-permeable form of Fura 2 (Fura 2-AM). (3) The concentrations of cGMP and eNO synthase (eNOS) were measured in endothelial cell intact strips. RESULTS: (1) In PE, endothelium-dependant (by BK) and -independent (by SNP) relaxation of NO in the STA2-induced contractions were significantly smaller, while the action of c GMP was also reduced. (2) BK increased the concentration of [Ca(2+)]i, although the increase was not reduced in PE. (3) The concentrations of cGMP with BK and without BK and eNOS were not reduced in PE. CONCLUSION: These results revealed that the action of endothelial NO might be reduced not due to decrease in the production of NO in the endothelium but rather to reduced action of cGMP itself.

PP062. Characteristic changes of systemic blood pressure in eclampsia.

AIM: It was found that eclampsia might be caused by vasogenic edema of brain as the results of breaking autoregulation of cerebral blood flow due to possibly the systemic increase in blood pressure (BP). In the present study, we investigated characteristic changes of systemic BP just after the onset of eclampsia. METHOD: Four eclamptic women during pregnancy were participated. Two had labor pains. Two were given anti-hypertensive drugs due to severe hypertension. BP in both systolic and diastolic, and mean arterial pressure (MAP), before and after onset of eclampsia were evaluated. RESULT: Basal BP in systolic, diastolic and MAP before eclampsia were 132±13, 79±24, 90±20mmHg. Maximum BP in systolic, diastolic and MAP before eclampsia were 172±10, 96±13 and 121±10mmHg. BP in systolic, diastolic and MAP after eclampsia were 124±23, 74±14 and 91±12mmHg. An increase in MAP was 24±11mmHg before eclampsia, while a decrease was 31±2mmHg after onset of eclampsia. CONCLUSION: In eclampsia, an increase in BP was seen just before eclampsia, while a severe decrease in BP (more than 30mmHg of MAP) was seen after it.

Glycogen storage disease type Ia (GSD Ia) during pregnancy: report of a case complicated by fetal growth restriction and preeclampsia.

Glycogen storage disease type Ia (GSD Ia) leads to disturbed glycogenolysis and gluconeogenesis due to a deficiency in the enzyme glucose-6-phosphatase. A patient with GSD Ia showed hypoglycemia and proteinuria without dietary management since early pregnancy. The patient's condition was complicated by hypertension with increase in proteinuria at 22 weeks of gestation. In spite of administration of antihypertensive drugs and dietary management, the disease became more severe with deterioration in the fetal status and inhibition of fetal growth. Thus, a cesarean section was performed at 26 weeks of gestation. The delivered male infant weighing 412 g died at 2 days after birth. The patient's blood pressure had normalized within 3 months after delivery, while proteinuria persisted.

The biological investigation of prostacyclin in preeclamptic women seen reduced endothelial function.

OBJECTIVE: Our aim was to determine the biological investigation of prostacyclin in preeclamptic women seen reduced endothelial vasodilatation by non-invasive technique in vivo. METHODS: Using a high resolution ultrasound transducer, diameters of brachial arteries were determined after reactive hyperemia in 15 non-pregnant, 20 normotensive pregnant and 20 preeclamptic women. The concentrations of 6-keto-prostaglandin F 1alpha (6keto-PGF 1alpha) in plasma and the concentrations of adenosine-3', 5'-cyclic monophosphate (cyclic AMP) in platelets and serum were measured among the groups. RESULTS: Flow-mediated vasodilatation at 1 min after reactive hyperemia was higher in normotensive pregnant than in the non-pregnant or preeclamptic women. The plasma concentration of 6 keto-PGF 1alpha as well as the serum concentration of cyclic AMP were lower in preeclamptic than those in normotensive pregnant women. The increase in cyclic AMP in the presence of a prostacyclin analogue in platelets was seen at similar levels in all three groups. CONCLUSION: From these results, the concentrations of prostacyclin in plasma and cyclic AMP in serum might be low possibly due to reduced production of prostacyclin in preeclamptic women seen reduced endothelial function.

Establishment of a polymerase chain reaction method for detection of Escherichia coli in amniotic fluid in patients with chorioamnionitis.

OBJECTIVE: We investigated whether Escherichia coli could be detected by E. coli of reference (ECOR) grouping and virulence factors (VFs) in amniotic fluid using polymerase chain reaction (PCR). METHOD: From 18 patients with clinical symptoms, such as cyclic uterine contraction, genital bleeding and cervical ripening, who subsequently developed abortion or labor before term, and from 40 normal pregnant women undergoing diagnostic amniocentesis, amniotic fluid was obtained. All samples were negative for standard culture. Six patients with symptoms were classified into the ECOR group, and with VFs, E. coli was detected in 6 patients. Thus, 4 patients were positive for both tests. CONCLUSION: We could establish a detection method for E. coli in amniotic fluid using both ECOR grouping and VFs with PCR.

Increase in serum concentrations of inhibin in early onset pre-eclampsia with intrauterine growth restriction.

AIM: Recently, it has been hypothesized that reduced placental blood flow in early pregnancy causes changes in endothelial function, leading to pre-eclampsia. To clarify this clinically, we assessed serum concentrations of inhibin and uric acid in pre-eclamptic women compared with those of normotensive pregnant women. METHODS: One hundred and forty normotensive pregnant women (at 20-41 weeks' gestation) and 50 women with pre-eclampsia (at 24-41 weeks' gestation) were the study subjects. Pre-eclamptic women were classified according to the new criteria for pregnancy-induced hypertension produced by the Japanese Society of Obstetrics and Gynecology (JSOG). Serum concentrations of uric acid and inhibin were measured enzymatically and by radioimmunoassay, respectively. RESULTS: Serum concentrations of inhibin and uric acid in the pre-eclamptic women were significantly higher than in gestational age-matched normotensive pregnant women. There were significant correlations among inhibin and uric acid, blood pressure and birth weight. According to JSOG criteria, of the 50 pre-eclamptic women, 18 were early onset (EO), including 16 cases complicated by intrauterine growth restriction (IUGR), and 32 cases were late onset, including 12 cases complicated by IUGR. In the patients with EO and IUGR, serum concentrations of inhibin, but not uric acid, were significantly elevated as compared with those of the other pre-eclamptic women. CONCLUSION: The results suggest that an increase in the serum concentration of inhibin seen in EO pre-eclampsia, together with IUGR, might be a cause of reduced placental blood flow.

Evaluation levels of cytokines in amniotic fluid of women with intrauterine infection in the early second trimester.

Amniotic fluid was obtained from 180 patients by amniocentesis at 16-22 weeks of gestation and assayed for the levels of interleukin (IL)-6, IL-8, leukocyte elastase (LE), and glucose. Ten of cases had clinical symptoms, such as uterine contraction, genital bleeding, and cervical ripening, and the other 170 were assessed for fetal chromosomal features. Four of the ten cases with uterine contraction developed abortion, while 10 of those screened had findings of fetal chromosomal anomalies, and 7 cases then underwent induced abortion artificially. In the cases of abortion, levels of IL-6, IL-8 and LE were higher than in the samples from the 160 pregnant women without clinical symptoms and a normal karyotype, while glucose in amniotic fluid was lower. Of 6 cases with clinical symptoms, but not developing abortion, 4 developed preterm labor, and in these IL-6 and IL-8 also were significantly elevated, with LE being slight high compared to normal. The results suggest that IL-6, IL-8, LE, and glucose in amniotic fluid at early second trimester can be used as markers of severe infection in the uterus, and with the first two being particularly sensitive.

Reduced nitric oxide in amniotic fluid of patients with chorioamnionitis.

OBJECTIVE: Levels of nitric oxide (NO) and cytokines were assessed in amniotic fluid obtained from patients with severe chorioamnionitis (CAM) and appropriate controls. METHODS: Amniotic fluid was obtained from 12 patients with CAM (17-24 weeks of gestation) and 89 patients undergoing diagnostic amniocentesis (16-18 weeks of gestation). The concentrations of NO, interleukin-6 (IL-6), and leukocyte elastase (LE) in amniotic fluid were then measured and compared. RESULTS: The concentrations of NO, IL-6, and LE were all higher in CAM cases than in normal pregnant women. Furthermore, an inverse correlation between NO and LE was suggested in the CAM group. CONCLUSIONS: These results indicate that in severe CAM, the action of NO might be reduced, not only due to blockage of action but also by degradation, despite increased production.

Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery.

We investigated whether 10 days' in vivo treatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteries ex vivo and, if so, what the underlying mechanism might be. ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric oxide-sensitive fluorescent dye diaminofluorescein-2) within the endothelial cells of rabbit mesenteric resistance arteries. This effect was significantly smaller in arteries isolated from NTG-treated rabbits than in those from control rabbits. The reduction in endothelial [NO]i in NTG-treated rabbits was prevented when olmesartan (blocker of type 1 angiotensin II receptors (AT1Rs)) was coadministered in vivo with NTG and also when the superoxide scavenger manganese (III) tetrakis-(4-benzoic acid) porphyrin (Mn-TBAP), the protein kinase C (PKC) inhibitor GF109203X or L-arginine (with or without the active form of folate (5-methyltetrahydrofolate)) was incubated with the arteries in vitro. Endothelial cell superoxide production (estimated by ethidium fluorescence) was greatly increased in arteries from NTG-treated rabbits. This was normalized by in vivo coadministration of olmesartan with NTG and also by in vitro application of Mn-TBAP or GF109203X (but not of 5-methyltetrahydrofolate+L-arginine). ACh increased the intracellular Ca2+ concentration (estimated using the Ca2+-sensitive dye Fura 2) within endothelial cells, the increase being not significantly different between NTG-treated rabbits and control rabbits. We conclude that in NTG-treated rabbits, endothelial nitric oxide production in mesenteric resistance arteries is reduced, possibly through a reduction in the bioavailability of L-arginine via an action mediated by superoxide. Activation of the AT1R-PKC pathway may be involved in increasing superoxide production.

Reduced hyperpolarization in endothelial cells of rabbit aortic valve following chronic nitroglycerine administration.

This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the hyperpolarization induced by acetylcholine (ACh) in aortic valve endothelial cells (AVECs) of the rabbit and, if so, whether antioxidant agents can normalize this downregulated hyperpolarization. ACh (0.03-3 microM) induced a hyperpolarization through activations of both apamin- and charybdotoxin-sensitive Ca2+-activated K+ channels (K(Ca)) in rabbit AVECs. The intermediate-conductance K(Ca) channel (IK(Ca)) activator 1-ethyl-2-benzimidazolinone (1-EBIO, 0.3 mM) induced a hyperpolarization of the same magnitude as ACh (3 microM). The ACh-induced hyperpolarization was significantly weaker, although the ACh-induced [Ca2+]i increase was unchanged, in NTG-treated rabbits (versus NTG-untreated control rabbits). The hyperpolarization induced by 1-EBIO was also weaker in NTG-treated rabbits. The reduced ACh-induced hyperpolarization seen in NTG-treated rabbits was not modified by in vitro application of the superoxide scavengers Mn-TBAP, tiron or ascorbate, but it was normalized when ascorbate was coadministered with NTG in vivo. Superoxide production within the endothelial cell (estimated by ethidium fluorescence) was increased in NTG-treated rabbits and this increased production was normalized by in vivo coadministration of ascorbate with the NTG. It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide.

Reduced flow-mediated vasodilation is not due to a decrease in production of nitric oxide in preeclampsia.

OBJECTIVE: Our aim was to determine the reduced function of endothelial nitric oxide in preeclampsia by use of noninvasive techniques in vivo. STUDY DESIGN: With the use of a high-resolution ultrasound transducer, diameters of brachial artery were measured after reactive hyperemia in 20 nonpregnant women, 20 normotensive pregnant women, and 15 women with preeclampsia. The concentrations of cyclic guanosine monophosphate were measured in samples of platelets from all groups. RESULTS: Flow-mediated vasodilation at 1 minute after deflation was higher in the normotensive pregnant women (115.1% +/- 6.5%) than in the nonpregnant women (108.7% +/- 3.9%); flow-mediated vasodilation was lower in women with preeclampsia (106.8% +/- 2.7%) than in the normotensive pregnant women. The concentration of platelet cyclic guanosine monophosphate was higher in the normotensive pregnant women than in the nonpregnant women (2.21 +/- 1.10 pmol/mL/10(8) cells vs 0.746 +/- 0.381 pmol/mL/10(8) cells). There was no difference between the normotensive pregnant and the preeclamptic group (2.81 +/- 1.82 pmol/mL/10(8) cells). Furthermore, the increase in cyclic guanosine monophosphate by sodium nitroprusside in platelet samples that were obtained from the normotensive pregnant women was larger than the samples from the nonpregnant women (6.20 +/- 4.2 pmol/mL/10(8) cells vs 1.62 +/- 0.81 pmol/mL/10(8) cells). The increase in cyclic guanosine monophosphate from the women with preeclampsia did not differ from that in the normotensive pregnant women (5.84 +/- 3.73 pmol/ml/10(8) cells). CONCLUSION: These results indicate that reduced endothelial nitric oxide activity might be due to a reduction of nitric oxide-cyclic guanosine monophosphate activity rather than its production in preeclampsia.

Use of aspirin and low-molecular-weight heparin to prevent recurrence of maternal floor infarction in women without evidence of antiphospholipid antibody syndrome.

During pregnancy, maternal floor infarction (MFI) and massive perivillous fibrin deposition (MFD) often cause fetal growth restriction and death, both being markedly increased by occlusion of the maternal intravenous circulation. Incident rates have been reported to be in the range of 0.09-0.5% and recurrent MFI/MFD might be more frequent in early-onset cases. Thus, prevention measures are necessary for high-risk women who have had MFI/MFD as complications in a previous pregnancy. In this report, the use of oral low-dose aspirin at the early trimester and low-molecular-weight heparin drip infusion from the mid-second trimester was examined for this purpose.

Cardiac failure caused by severe pre-eclampsia with placental abruption, and its treatment with anti-hypertensive drugs.

Pre-eclampsia is the abnormality of blood circulation in late pregnancy, often caused by renal failure, hemolysis, elevated liver enzyme, low platelet syndrome, and eclampsia. We present a case of severe pre-eclampsia with placental abruption in a 24-year-old woman, pregnant for the first time. The patient was diagnosed with congestive heart failure, which came as a result of pre-eclampsia. Anti-hypertensive drugs were used for its treatment.

Ultrastructural changes in omental resistance artery in women with preeclampsia.

OBJECTIVE: The reduced function that is played by the endothelium has been suggested in the pathophysiologic condition of resistance arteries during preeclampsia. Our aim was to determine whether morphologic changes occur in these arteries in patients with preeclampsia. STUDY DESIGN: The omental resistance arteries were isolated from 11 women with preeclampsia and 10 normotensive pregnant women; the preparations were analyzed by light and electron microscopy. RESULTS: On light microscopic examination, no differences were apparent between both groups of women in cross-sectional preparations of the omental resistance arteries. However, after electron microscopic examination, characteristic changes were found in the subendothelial region of the resistance arteries from women with preeclampsia compared with specimens from normotensive pregnant women. The thickness of elastic lamina was irregular, and the basement membrane was, in part, incomplete. Thus, the arrangement of the location of endothelial cells was changed in the resistance arteries that were taken from women with preeclampsia. CONCLUSION: These results indicate that ultrastructural changes develop in the subendothelial region of omental resistance arteries in women with preeclampsia.

Involvement of H2O2 in superoxide-dismutase-induced enhancement of endothelium-dependent relaxation in rabbit mesenteric resistance artery.

1 The mechanism underlying the enhancement by superoxide dismutase (SOD) of endothelium-dependent relaxation was investigated in rabbit mesenteric resistance arteries. 2 SOD (200 U ml(-1)) increased the production of H(2)O(2) in smooth muscle cells (as indicated by the use of an H(2)O(2)-sensitive fluorescent dye). 3 Neither SOD nor catalase (400 U ml(-1)) modified either the resting membrane potential or the hyperpolarization induced by acetylcholine (ACh, 1 micro M) in smooth muscle cells. 4 In arteries constricted with noradrenaline, the endothelium-dependent relaxation induced by ACh (0.01-1 micro M) was enhanced by SOD (200 U ml(-1)) (P<0.01). This action of SOD was inhibited by L-N(G)-nitroarginine (nitric oxide (NO)-synthase inhibitor) but not by either charybdotoxin+apamin (Ca(2+)-activated-K(+)-channel blockers) or diclofenac (cyclooxygenase inhibitor). 5 Neither ascorbate (50 micro M) nor tiron (0.3 mM), superoxide scavengers, had any effect on the ACh-induced relaxation, but each attenuated the enhancing effect of SOD on the ACh-induced relaxation. Similarly, catalase (400 U ml(-1)) inhibited the effect of SOD without changing the ACh-induced relaxation. 6 In endothelium-denuded strips constricted with noradrenaline, SOD enhanced the relaxation induced by the NO donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7) (P<0.05). Ascorbate and catalase each attenuated this effect of SOD. 7 H(2)O(2) (1 micro M) enhanced the relaxation on the noradrenaline contraction induced by NOC-7 and that induced by 8-bromo-cGMP, a membrane-permeable analogue of guanosine 3',5' cyclic monophosphate (cGMP). 8 SOD had no effect on cGMP production, whether measured in endothelium-intact strips following an application of ACh (0.1 micro M) or in endothelium-denuded strips following an application of NOC-7 (0.1 micro M). 9 It is suggested that in rabbit mesenteric resistance arteries, SOD increases the ACh-induced, endothelium-dependent relaxation by enhancing the action of NO in the smooth muscle via its H(2)O(2)-producing action (rather than via a superoxide-scavenging action).

Reduced function of endothelial prostacyclin in human omental resistance arteries in pre-eclampsia.

It remains unclear in pre-eclampsia whether or not a functional change occurs in the role played by prostacyclin in endothelium-dependent relaxation in resistance arteries. We examined this using human omental resistance arteries (obtained from pre-eclamptic or normotensive pregnant women) in the presence of N(G)-nitro-L-arginine (L-NNA, an inhibitor of nitric oxide synthase). In endothelium-intact strips from both groups, 9,11-epithio-11,12-methano-thromboxane A(2) (STA(2), a thromboxane A(2) mimetic) produced a contraction. Diclofenac (an inhibitor of cyclooxygenase) enhanced the STA(2) contraction only in the normotensive pregnant group (1.4 times control, P < 0.01). In the presence of STA(2), bradykinin (0.1 microM) produced an endothelium-dependent relaxation in both groups, the relaxation being significantly smaller for the pre-eclamptic group (P < 0.002). Diclofenac significantly attenuated the bradykinin-induced relaxation only for the normotensive pregnant group (31 % inhibition, P < 0.001). The bradykinin-induced membrane hyperpolarization consisted of diclofenac-sensitive and -insensitive components. The former, but not the latter, was significantly smaller in pre-eclampsia (-4.3 vs. -2.6 mV, P < 0.05). The concentrations of 6-keto-PGF(1alpha) (a stable metabolite of prostacyclin) in these arteries were significantly lower in pre-eclampsia in both the absence and presence of bradykinin (about 0.2-0.4 times the normotensive pregnant value in each case, P < 0.01). By contrast, both the relaxation and the membrane hyperpolarization in response to beraprost (10 nM, a stable analogue of prostacyclin) were similar between the two groups. We conclude that, in pre-eclampsia, a reduced part is played by prostaglandins in the endothelium-dependent relaxation seen in resistance arteries and that this may be due to a reduced production of prostacyclin by the endothelium.