The effects of a cyclo-oxygenase II inhibitor on placental artery production of thromboxane and prostacyclin

OBJECTIVE: The study was undertaken to determine the effects of a cyclo-oxygenase II inhibitor on fetoplacental artery production of prostacyclin and thromboxane A(2). STUDY DESIGN: Eight placentas were obtained from normal parturients at delivery and four chorionic plate arteries were dissected from each placenta. Arteries were incubated in media alone, media plus angiotensin II (1x10(-10) mol), media plus rofecoxib (300 ng/mL), or media plus angiotensin II and rofecoxib. Serial samples were assayed for metabolites of thromboxane B(2) and prostacyclin by enzyme-linked immunosorbent assay. Results were compared by analysis of variance, and P<.05 was considered significant. RESULTS: At 24 hours, 6-keto-prostaglandin F(1alpha) levels in the rofecoxib group (1.74+/-1.39 ng/mg tissue, P<.01) and the rofecoxib plus angiotensin II group (2.15+/-1.85 ng/mg tissue, P<.01) were significantly lower than levels in the control group (4.25+/-2.03 ng/mg tissue). Thromboxane B(2) levels were lower in the angiotensin II group (0.65+/-0.33 ng/mg tissue) than the control group (1.22+/-0.70 ng/mg tissue, P<.05). CONCLUSION: Cyclo-oxygenase II inhibition decreases the production of prostacyclin in fetoplacental arteries and alters the normal ratio of thromboxane A(2) to prostacyclin.     

Preeclampsia: an imbalance in placental prostacyclin and thromboxane production

Preeclampsia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation, reduced uteroplacental blood flow, and premature delivery. Because prostacyclin antagonizes the vasoconstrictor, platelet-aggregating, and uterine-activating actions of thromboxane, we considered the hypothesis that placental production of thromboxane was increased coincident with decreased production of prostacyclin in preeclampsia. Fresh human term placentas were obtained immediately after delivery from 11 normal and 10 preeclamptic pregnancies (blood pressure greater than or equal to 140/90 mm Hg, urinary protein greater than 0.3 gm/24 hr). Tissues (350 mg) were incubated sterilely in 6 ml of Dulbecco's Modified Eagle's Medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32, and 48 hours and analyzed for thromboxane by radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1 alpha. The production of thromboxane was significantly increased in preeclamptic versus normal placental tissue (22.9 +/- 4.7 versus 6.3 +/- 1.5 pg/mg/hr, mean +/- SE, p less than 0.01), whereas the production of prostacyclin was significantly decreased (3.0 +/- 0.3 versus 6.7 +/- 0.5 pg/mg/hr, p less than 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 mumol/L) and not affected (p greater than 0.50) by arachidonic acid (100 mumol/L). Therefore, during normal pregnancy, the placenta produces equivalent amounts of thromboxane and prostacyclin, so that their biologic actions on vascular tone, platelet aggregation, and uterine activity will be balanced. In preeclamptic pregnancy, however, the placenta produces seven times more thromboxane than prostacyclin.     

Prevention of Pre-eclampsia: Low-dose Aspirin,Calcium and Antioxidants

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Early deliver remains the only effective treatment for this condition. The purpose of this article is to review the role of low-dose aspirin and calcium supplements and to address the potential role of antioxidants in the prevention of pre-eclampsia.Early studies and meta-analysis suggested that low-dose aspirin reduced the incidence of pre-eclampsia. In more recent reports, large clinical trials studying health nulliparous women and women at higher risk for pre-eclampsia have shown that low-dose aspirin has little effect. Calcium supplements also ail to reduce the risk of developing pre-eclampsia in nulliparous women. Recent findings support the hypothesis that “oxidative stress” may be involved in the pathogenesis of pre-eclampsia. This has led to the suggestion that antioxidant therapy may be beneficial. The disappointing results of the large trials of aspirin and calcium suggest that better support for the role of oxidative stress should be available before such trials are undertaken.In summary, large clinical trials have not supported the encouraging results of smaller trials and meta-analysis. There is little evidence that low-dose aspirin or calcium is effective or the prevention of pre-eclampsia. Further advances in preventative therapy await a more thorough understanding of the pathophysiology of the disease process.     

Comparison of two-risk assessment algorithms for preeclampsia in first trimester with consecutive intake of low-dose aspirin in the high-risk group – an observational study

We analyzed outcome of women screened for preeclampsia with two different multifactorial risk algorithms (Predictor^®Software by PerkinElmer, PerkinElmer, Waltham, MA; PERK-group: n?=?214 and Viewpoint^® by GE Healthcare, Dornstadt, Germany; VIEW-group: n?=?209) in first trimester. Women at high risk for developing preeclampsia were advised to take low-dose acetylsalicylic acid (LDA). Screening positive rates for early onset preeclampsia differed significantly between the two groups (7.9% versus 26.3%; p?=?0.000). According the clinical use of screening test criteria, LDA was prescribed in 63 (29.4%) women in the PE-group and 55 (26.3%) in the VP-group (p?=?0.516). There were no differences in onset of preeclampsia [4 (1.9%) versus 6 (2.9%); p?=?0.540]. No early or severe preeclampsia occurred in the whole population.     

Do prostacyclin and thromboxane contribute to the “protective effect” of pregnancies with chronic hypertension? A preliminary prospective longitudinal study

OBJECTIVE: The aim of this study was to assess prospectively the urinary excretion of renal and systemic metabolites of thromboxane and prostacyclin in normotensive and chronic hypertensive pregnancies. STUDY DESIGN: Pregnant hospital employees were invited to collect 24-hour urine samples weekly from the seventh week until delivery. Concentrations of renal metabolites (thromboxane B₂, 6-keto-prostaglandin F_1α) were measured by radioimmunoassay after extraction. Systemic metabolites (2,3-dinor-thromboxane B₂, 2,3-dinor-6-keto-prostaglandin F_1α) were assessed by enzyme immunoassay after extraction and high-pressure liquid chromatographic separation. RESULTS: Thromboxane B₂ excretion was similar in normotensive and hypertensive pregnancies, whereas a twofold increase of 6-keto-prostaglandin F_1α was observed in hypertensive compared with normotensive pregnancies (7537 ± 349 vs 3857  ± 202 pg/mg creatinine, p < 0.001). During pregnancy in both conditions measurements displayed uniform excretion of thromboxane B₂ with progressively increased levels of 6-keto-prostaglandin F_1α in chronic hypertension (R² = 0.60, p < 0.005). Mean excretion of 2,3-dinor-thromboxane B₂ averaged 1208 ± 65 and 898 ± 48 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mainly due to significant decreased concentrations in hypertension in the first half of pregnancy. Conversely, 2,3-dinor-6-keto-prostaglandin F_1α levels were 845 ± 39 and 1226 ± 67 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mostly because of significantly increased production in hypertension from 22 weeks onward. Ratios of both renal and systemic metabolites favored increased prostacyclin production in chronic hypertension. CONCLUSION: In contrast to preeclampsia, uncomplicated mild to moderate chronic hypertensive pregnancies are characterized by an excess production of prostacyclin with unaltered or even lower thromboxane concentrations, which may contribute to the general favorable outcome of this hypertensive condition.(Am J Obstet Gynecol 1997;177:1483-90.)     

Protein S deficiency complicated pregnancy in women with recurrent pregnancy loss

This prospective study aimed to evaluate pregnancy outcome and complications in women with recurrent pregnancy loss (RPL) and protein S (PS) deficiency, who received low dose aspirin (LDA) or LDA plus heparin (LDA/H) therapies. Clinical characteristics, pregnancy outcome and complications of 38 women with two or more RPL and?<60% of plasma free PS antigen were compared among three groups: antiphospholipid antibody (aPL)-negative women who received LDA (group A), aPL-negative women who received LDA/H (group B) and aPL-positive women who received LDA/H (group C). Gestational weeks (GW) at delivery in group C (median 32?GW) were earlier than 40?GW in group A and 38.5?GW in group B (p?p?p<0.05). Women with RPL, PS deficiency, and positive aPL had high risks for adverse pregnancy outcome and complications, even when they received LDA/H therapy. Among women with RPL, PS, and negative aPL, there was no difference in these risks between LDA alone and LDA/H therapies.     

Measurements of Blood Pressure, Oedema and Proteinuria in a Pregnant Population of New Zealand

Summary: This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that Mood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Ffg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of >33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women. Ankle oedema was significantly associated with the development of both gestational hypertension and preeclampsia but the incidence of oedema was noted in only 11.9% of the subjects.     

Seasonal Variation in Gestational Blood Pressure

Objective: To assess seasonal variability in antenatal blood pressure (BP). Methods: We studied 1919 pregnant women who contributed 21,119 antenatal BP measurements. Results: BP peaked in winter and reached a nadir in summer. After confounder adjustment, systolic BP was 1.0 to 1.7 mm Hg higher January to May, 0.6 mm Hg higher in September and October, and 0.8 mm Hg higher in November and December compared with August. After stratifying by overweight status, BP showed strong seasonal variability among lean women, whereas there were no seasonal trends among overweight women. Conclusion: Environmental factors may regulate gestational BP and may be relevant to seasonality of hypertensive disorders of pregnancy.     

Errors in the Measurement of Blood Pressure

Summary: The effect of posture on blood pressure measurement in pregnant and non-pregnant subjects was studied. In non-pregnant patients undergoing cardiac catheterization, central blood pressure remained unaltered with a change from the supine to the lateral position. However in all subjects studied, an apparent decrease in both systolic and diastolic blood pressure occurred when measured in the upper arm in the lateral position. This fall is artifactual and does not represent a change in blood pressure.
It is concluded that blood pressure measurements in the lateral position are inaccurate.     

Blood Pressure Assessments in Different Subtypes of Hypertensive Pregnant Women: Office Versus Home Patient- or Nurse-Measured Blood Pressure

Objective:?To explore the difference between distinct methods of assessing blood pressure (BP) in pregnant women with different hypertensive disorders.?Methods:?We compared office BP to home patient- and nurse-measured diastolic BP in pregnant women with essential chronic hypertension (CH), preeclampsia (PE) and isolated hypertension (IOH).?Results:?Office BP was lower or similar to home patient- and nurse-measured BP in women with CH. Office BP was higher than home patient-measured BP in women with PE and in women with IOH (p < 0.0001). Nurse-measured BP was higher than patient-measured BP in women with PE (p < 0.01).?Conclusions:?BP assessments in women with PE are significantly influenced by the environment, which should be considered in managing these women.     

Accuracy of Automated Blood Pressure Recorders in Pregnancy

Summary: Automated blood pressure recorders are used with increasing frequency by pregnant women, mostly without proper evaluation of their accuracy. We compared blood pressures (BP) recorded by 2 automated noninvasive devices, the Spacelabs 90207 ambulatory blood pressure monitor and the OMRON HEM 705 CP portable selfinitiated device, with blood pressures recorded by routine sphygmomanometry in 79 pregnant women either considered 'at risk' for preeclampsia or with mild hypertension in pregnancy. The Spacelabs device tended to overestimate systolic BP by a mean 11 (SD = 8) mmHg and diastolic BP by 5 (SD = 7) mmHg for phase 5 pressure (p < 0.001) but was similar to routine BPs for diastolic phase 4 pressures. The OMRON device tended to underestimate diastolic (phase 4) pressure by 4 (SD = 6) mmHg (p < 0.001) but gave similar systolic and diastolic (phase 5) pressures to routine sphygmomanometry. However, for both devices there was considerable individual patient variability in accuracy. When using these devices to record a limited number of blood pressure recordings, as in this study, we suggest that individual comparison with mercury sphygmomanometry be made in each pregnant woman before accepting the validity of these recordings.     

Gestational Blood Pressure Monitoring and its Chronobiometric Quantification

Blood pressure (BP) monitoring is a clinical reality because of the availability of non-invasive automated recorders. BP 24-h patterns were explored during physiologic pregnancies in order to obtain time-qualified standards for clinical use. Non-inferential and inferential reference boundaries were computed by using chronobiometric procedures. The computed confidence limits provide a set of reference standards that serves to optimize the diagnosis of pregnancy-induced deviation in BP 24-h patterns.     

Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial

IntroductionThe effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown.AimTo examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension.MethodsWe performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of <120 mmHg) or a standard treatment group (SBP goal of <140 mmHg).Main Outcome MeasureThe main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years.ResultsAt baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction = 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference = 0.67; 95% CI = 0.03, 1.32; P = 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference = −1.17; 95% CI = −1.92, −0.41; P = 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P > 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P = 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P = 0.53) and was without interaction by race-ethnicity.Clinical ImplicationsThe effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude.Strength & LimitationsAlthough this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed.ConclusionIn a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude.Foy CG, Newman JC, Russell GB, et al. Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. J Sex Med 2020;17:238–248.     

Circadian Pattern of Blood Pressure in Normal Pregnancy and Preeclampsia

Aims &; Objective

To find out the circadian pattern of blood pressure in normotensive pregnant women and in women with preeclampsia.

Method

A cross-sectional prospective observational case control study. Blood pressure was sampled in thirty-five normotensive pregnant women (control) and thirty five preeclamptic women (study group) by using non-invasive automatic ambulatory blood pressure monitoring machine for 72 h.

Results

Blood pressure (BP) was not constant over 24 h period and it oscillated from time to time in control group. BP was maximum during early part of afternoon. However, in preeclampsia besides quantitative increase in BP, circadian BP oscillations were less pronounced and in around 50% subjects BP was maximum during evening and night hours.

Conclusion

Both systolic and diastolic BP showed definite reproducible circadian pattern in both preeclamptic and normotensive pregnant women. This pattern both quantitatively and qualitatively was different in preeclamptic women. Standardized 24 h BP monitoring allows quantitative and qualitative evaluation of hypertensive status and is important for timing and dosing of antihypertensive medications.     

正常血压子痫21例临床分析

目的 :探讨正常血压子痫的共同临床特征和结局 ,并提出如何提高此种类型子痫的临床诊断及防治对策。方法 :对 2 1例正常血压子痫病例进行临床及实验室结果的回顾性分析。结果 :2 1例子痫中抽搐前血压均正常 ,但抽搐前半数以上的病例有自觉症状 (12例 )、高血粘度 (16例 )、蛋白尿 (16例 )、水肿 (12例 )。结论 :对血压正常的孕产妇 ,不能完全排除妊高征的可能