"Third drug" trial: comparative study of antihypertensive agents added to treatment when blood pressure remains uncontrolled by a beta blocker plus thiazide diuretic.

Hydralazine, labetalol, methyldopa, minoxidil, prazosin, and placebo were compared when added by random allocation to atenolol 100 mg and bendrofluazide 5 mg daily in a series of 238 hypertensive patients inadequately controlled by the beta blocker-diuretic combination. Atenolol was withdrawn in those allocated to labetalol, and minoxidil was given only to men. The order of acceptability was: placebo, hydralazine, prazosin, methyldopa, minoxidil, labetalol. Minoxidil was more effective than the other active drugs, which had similar potency to one another. All the active agents were more effective than placebo. Hydralazine was the most generally suitable third drug, with prazosin a close second. Minoxidil was especially effective in patients with less severe hypertension but the same regimen caused fluid retention in those with more severe disease. Labetalol should probably be introduced at a low dose (150 mg daily) even when replacing full doses of a previously administered beta blocker.     

Maternal Overweight and Obesity and Risks of Severe Birth-Asphyxia-Related Complications in Term Infants: A Population-Based Cohort Study in Sweden

Background

Maternal overweight and obesity increase risks of pregnancy and delivery complications and neonatal mortality, but the mechanisms are unclear. The objective of the study was to investigate associations between maternal body mass index (BMI) in early pregnancy and severe asphyxia-related outcomes in infants delivered at term (≥37 weeks).

Methods and Findings

A nation-wide Swedish cohort study based on data from the Medical Birth Register included all live singleton term births in Sweden between 1992 and 2010. Logistic regression analyses were used to obtain odds ratios (ORs) with 95% CIs for Apgar scores between 0 and 3 at 5 and 10 minutes, meconium aspiration syndrome, and neonatal seizures, adjusted for maternal height, maternal age, parity, mother''s smoking habits, education, country of birth, and year of infant birth. Among 1,764,403 term births, 86% had data on early pregnancy BMI and Apgar scores. There were 1,380 infants who had Apgar score 0–3 at 5 minutes (absolute risk  = 0.8 per 1,000) and 894 had Apgar score 0–3 at 10 minutes (absolute risk  = 0.5 per 1,000). Compared with infants of mothers with normal BMI (18.5–24.9), the adjusted ORs (95% CI) for Apgar scores 0–3 at 10 minutes were as follows: BMI 25–29.9: 1.32 (1.10–1.58); BMI 30–34.9: 1.57 (1.20–2.07); BMI 35–39.9: 1.80 (1.15–2.82); and BMI ≥40: 3.41 (1.91–6.09). The ORs for Apgar scores 0–3 at 5 minutes, meconium aspiration, and neonatal seizures increased similarly with maternal BMI. A study limitation was lack of data on effects of obstetric interventions and neonatal resuscitation efforts.

Conclusion

Risks of severe asphyxia-related outcomes in term infants increase with maternal overweight and obesity. Given the high prevalence of the exposure and the severity of the outcomes studied, the results are of potential public health relevance and should be confirmed in other populations. Prevention of overweight and obesity in women of reproductive age is important to improve perinatal health. Please see later in the article for the Editors'' Summary     

The lupus syndrome induced by hydralazine: a common complication with low dose treatment.

The true incidence of the lupus syndrome induced by hydralazine was determined in a longitudinal study of 281 patients consecutively starting hydralazine for hypertension over a 51 month period. Data on the duration of treatment and the maximum dose achieved were examined using life table analysis. After three years'' treatment with hydralazine the incidence of the lupus syndrome was 6.7% (95% confidence limits 3.2-10.2%). The incidence was dose dependent, with no cases recorded in patients taking 50 mg daily and incidences of 5.4% with 100 mg daily and of 10.4% with 200 mg daily. The incidence was higher in women (11.6%) than in men (2.8%). In women taking 200 mg daily the three year incidence was 19.4%. Hydralazine is an effective antihypertensive drug that has come to be used in restricted dosage (not more than 200 mg daily) because of its risk of inducing the lupus syndrome. This study shows that the true incidence of the syndrome is still unacceptably high even when the drug is prescribed according to current recommendations.     

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis

Objective To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation.Design Systematic review and meta-analysis.Data sources Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists.Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients.Data synthesis Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77).Conclusions Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.     

Does routine ultrasound scanning improve outcome in pregnancy? Meta-analysis of various outcome measures.

OBJECTIVE--To evaluate the effectiveness of routine ultrasound scanning in pregnancy by a meta-analysis of various outcome measures. DESIGN--Meta-analysis of randomised controlled trials evaluating the effect of routine ultrasound scanning on perinatal mortality and morbidity. Live birth rate (that is, live births per pregnancy) is included as a measure of pregnancy outcome in addition to the conventional perinatal mortality. SUBJECTS--15,935 pregnancies (7992 in which routine ultrasound scanning was used and 7943 controls with selective scanning) from four randomised controlled trials. MAIN OUTCOME MEASURES--Perinatal mortality, live birth rate, rate of miscarriage, Apgar score < 7 at 1 minute, and number of induced labours. RESULTS--The live birth rate was identical in both screening and control groups (odds ratio = 0.99; 95% confidence interval 0.88 to 1.12) although the perinatal mortality was significantly lower in the group who had routine ultrasonography (0.64, 0.43 to 0.97). Differences in perinatal morbidity between the two groups as measured by the proportion of newborn babies with Apgar score < 7 at 1 minute were not significant (1.05; 0.93 to 1.19). CONCLUSION--Routine ultrasound scanning does not improve the outcome of pregnancy in terms of an increased number of live births or of reduced perinatal morbidity. Routine ultrasound scanning may be effective and useful as a screening for malformation. Its use for this purpose, however, should be made explicit and take into account the risk of false positive diagnosis in addition to ethical issues.     

Active management of severe pre-eclampsia

An active approach to the management of severe pre-eclampsia is outlined using sedation with diazepam, hypotensive therapy with hydralazine and immediate steps to terminate the pregnancy.Clinical experience with 80 cases is described. There was no maternal loss and corrected perinatal mortality was 4.8%.     

Nitrendipine and other calcium entry blockers (calcium antagonists) in hypertension

Nitrendipine is a calcium antagonistic 1,4-dihydropyridine derivative with a pronounced antihypertensive activity in animal experiment. Similar to other calcium entry blockers, nitrendipine decreases blood pressure by lowering the elevated peripheral vascular resistance. However, its long-term effect differs from that of vasodilators such as hydralazine and minoxidil. In contrast to vasodilators, nitrendipine reduces heart hypertrophy in various forms of experimental hypertension in rats. Nitrendipine is highly effective in normalizing blood pressure, reducing heart hypertrophy, and preventing mortality in salt-related hypertension (two-kidney renal hypertension, salt-induced hypertension in Dahl rats), which are rather refractory to the effect of vasodilators. Nitrendipine reduces renovascular resistance in spontaneously hypertensive rats but has no effect on that of normotensive rats. In conscious renal hypertensive dogs, nitrendipine decreases blood pressure more than does hydralazine. The reflex tachycardia is more pronounced after hydralazine than after nitrendipine; blood pressure decrease is greater and the duration of the effect is longer than that of nifedipine. Nitrendipine is thus predicted as an effective drug for antihypertensive monotherapy.     

硫酸镁联合硝苯地平治疗中重度妊娠高血压综合征患者的疗效观察

目的:探讨硫酸镁联合硝苯地平治疗中重度妊娠期高血压综合征的临床疗效。方法:选取2013年5月-2014年10月我院收治的中重度妊娠期高血压综合征患者70例,随机将患者分为研究组和对照组,每组35例。对照组患者应用硫酸镁治疗,研究组患者给予硫酸镁联合硝苯地平治疗,比较两组患者的临床疗效、血压变化、血液粘度、24 h尿蛋白含量以及血细胞压积情况。结果:研究组治疗总有效率显著优于对照组,差异具有统计学意义(P0.05);两组患者治疗后的血压水平显著低于治疗前,且研究组显著优于对照组,差异具有统计学意义(P0.05);两组患者治疗后的血液粘度、24 h尿蛋白含量及血细胞压积显著优于治疗前,且研究组优于对照组,差异具有统计学意义(P0.05)。结论:硫酸镁联合硝苯地平治疗中重度妊娠期高血压具有较好的临床疗效,能够显著改善患者的临床症状。     

Metabolism of hydralazine by rat hepatocytes

The metabolism of hydralazine and its pyruvic acid hydrazone was studied in a medium containing isolated adult rat hepatocytes. Hydralazine undergoes conversion to 3-methyltriazolophthalazine, while hydralazine pyruvic acid hydrazone is not metabolized in rat hepatocytes.     

慢性高血压合并妊娠发生子痫前期的危险因素分析

目的:探讨慢性高血压合并妊娠发生子痫前期的危险因素,为筛查慢性高血压孕妇合并子痫前期提供参考依据。方法:选取2009年3月~2013年7月我院收治的慢性高血压妊娠患者116例,根据是否合并子痫前期分为慢性高血压合并妊娠组(NHDP组)和慢性高血压合并子痫前期组(HDP组),比较两组患者不同孕期的血压、尿蛋白水平以及血液生化检测指标间的差异。结果:两组间年龄、孕次、孕前尿蛋白水平、孕早期及孕中期的平均动脉压、尿蛋白水平间差异均无统计学意义(P0.05)。HDP组孕前体质指数、孕晚期的平均动脉压、尿蛋白水平、Hb、UA、LDH、FDP均较NHPD组显著升高(P0.05),两组间Plt水平差异无统计学意义(P0.05)。logistic回归分析发现Hb、UA及FDP是慢性高血压妊娠患者并发子痫前期的危险因素。结论:凝血状况、血清尿酸水平及肾功能变化是慢性高血压合并妊娠者发生子痫前期的危险因素。     

Nifedipine prevents vascular endothelial dysfunction in a mouse model of obesity and type 2 diabetes, by improving eNOS dysfunction and dephosphorylation

The effect of calcium channel blockers (CCBs) on type 2 diabetes is still unclear. The present study was undertaken to examine the efficacy of nifedipine, a dihydropyridine CCB, on obesity, glucose intolerance and vascular endothelial dysfunction in db/db mice (a mouse model of obesity and type 2 diabetes). db/db mice, fed high-fat diet (HFD) were treated with vehicle, nifedipine (10 mg kg(-1) day(-1)) or hydralazine (5 mg kg(-1) day(-1)) for 4 weeks, and the protective effects were compared. Although nifedipine and hydralazine exerted similar blood pressure lowering in db/db mice, neither affected body weight, fat weight, and glucose intolerance of db/db mice. However, nifedipine, but not hydralazine, significantly improved vascular endothelial function in db/db mice, being accompanied by more attenuation of vascular superoxide by nifedipine than hydralazine. These protective effects of nifedipine were attributed to the attenuation of eNOS uncoupling as shown by the prevention of vascular endothelial nitric oxide synthase (eNOS) dimer disruption, and the prevention of dihydrofolate reductase (DHFR) downregulation, the key enzyme responsible for eNOS uncoupling. Moreover, nifedipine, but not hydralazine, significantly prevented the decreases in phosphorylation of vascular akt and eNOS in db/db mice. Our work provided the first evidence that nifedipine prevents vascular endothelial dysfunction, through the inhibition of eNOS uncoupling and the enhancement of eNOS phosphorylation, independently of blood pressure-lowering effect. We propose that nifedipine may be a promising therapeutic agent for cardiovascular complications in type 2 diabetes.     

Response to beta-blockers in maternal and fetal rat hearts in vitro.

The effects of beta-blockers on maternal and fetal heart rates have been assessed by comparing isoprenaline concentration-heart rate relationships of hearts isolated from pregnant rats. The normal and maximal heart rates obtained for the maternal and fetal hearts were similar to published data. A slightly but significantly higher concentration of isoprenaline was required to produce 50% of the maximal response of fetal hearts than maternal hearts, suggesting that fetal hearts were less sensitive to isoprenaline than the maternal hearts. The beta-blockers used (propranolol, labetalol, metoprolol and atenolol) all showed a lower affinity to the beta-receptors of fetal hearts than those of maternal hearts, as indicated by significant differences in the pA2 values. Given the similar effects of the beta-blockers in the maternal and fetal hearts it is concluded that pharmacokinetic considerations and beta-blocker selectivity should be used as the basis of choice when treating maternal hypertension during pregnancy.     

Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy.

Fifty-three pregnant women with moderately severe hypertension were randomly allocated to treatment with methyldopa or oxprenolol. There were no significant differences between the groups in age, height, weight, parity, or stage of gestation at the start of treatment. The outcome of pregnancy was better in the group treated with oxprenolol, with greater maternal plasma volume expansion and placental and fetal growth. No intrauterine deaths occurred in either group, and antepartum fetal distress, detected by oxytocin challenge testing, was evident in only one patient, who received methyldopa. This infant, and one other in the methyldopa group, died in the neonatal period. No neonatal deaths occurred in the oxprenolol-treated group. Even in this small number of patients these results were considerably better than those in untreated women with hypertension of similar severity. Apgar scores in both groups were equivalent at birth, while blood sugar concentrations were higher in the oxprenolol group. Oxprenolol appears to be safe and effective in controlling hypertension during pregnancy. There was no evidence of harmful effects on the fetus, and oxprenolol may offer a selective advantage over methyldopa for fetal growth and wellbeing in utero.     

Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy

OBJECTIVE: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. OPTIONS: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. OUTCOMES: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. EVIDENCE: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. VALUES: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. BENEFITS, HARMS AND COSTS: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. RECOMMENDATION: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. VALIDATION: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.     

Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa.

One hundred and eighty three hypertensive pregnant women were randomly assigned to antihypertensive treatment with oxprenolol (96 women) or methyldopa (87 women). Control of hypertension was equivalent in both treatment groups, and in 64 (35%) cases hydralazine had to be added to the treatment to achieve the therapeutic goal (diastolic blood pressure below 85 mm Hg). Five perinatal deaths occurred, one in the oxprenolol group and four in the methyldopa group. Detailed analysis confirmed a previous report of greater fetal growth in the group treated with oxprenolol; this trend was present regardless of severity of hypertension and parity. With increasing duration of treatment the differences between the two groups diminished, and there was no difference after 10 weeks of treatment, a finding that may explain some of the reported discrepancies among therapeutic studies. As hypertension in pregnancy may pursue an accelerated course, necessitating urgent delivery, and there is no satisfactory method of predicting the duration of treatment in individual patients fetal benefit is most likely to be achieved by treatment with oxprenolol, provided that there is no maternal contraindication to treatment with beta blockers.     

Pregnancy Incidence and Risk Factors among Women Participating in Vaginal Microbicide Trials for HIV Prevention: Systematic Review and Meta-Analysis

Introduction

Pregnancy is contraindicated in vaginal microbicide trials for the prevention of HIV infection in women due to the unknown maternal and fetal safety of the microbicides. Women who become pregnant are taken off the microbicide during pregnancy period but this result in reduction of the power of the trials. Strategies to reduce the pregnancy rates require an understanding of the incidence and associated risk factors of pregnancy in microbicide trials. This systematic review estimates the overall incidence rate of pregnancy in microbicide trials and describes the associated risk factors.

Methods

A comprehensive literature search was carried out to identify eligible studies from electronic databases and other sources. Two review authors independently selected studies and extracted relevant data from included studies. Meta-analysis of incidence rates of pregnancy was carried out and risk factors of pregnancy were reported narratively.

Results

Fifteen studies reporting data from 10 microbicide trials (N=27,384 participants) were included. A total of 4,107 participants (15.0%) fell pregnant and a meta-analysis of incidence rates of pregnancy from 8 microbicide trials (N=25,551) yielded an overall incidence rate of 23.37 (95%CI: 17.78 to 28.96) pregnancies per 100 woman-years. However, significant heterogeneity was detected. Hormonal injectable, intra-uterine device (IUD) or implants or sterilization, older age, more years of education and condom use were associated with lower pregnancy. On the other hand, living with a man, history of pregnancy, self and partner desire for future baby, oral contraceptive use, increased number of unprotected sexual acts and inconsistent use of condoms were associated with higher pregnancy.

Conclusions

The incidence rate of pregnancy in microbicide trials is high and strategies for its reduction are urgently required in order to improve the sample size and power of these trials.     

The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis

ABSTRACT: Chronic hepatitis B virus (HBV) infection poses a serious public health problem in many parts of the world. Presently, even with proper joint immunoprophylaxis, approximately 10-15% of newborns from HBV carrier mothers suffer from HBV infection through intrauterine transmission. One of the risk factors is the level of maternal viraemia. Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV. A few studies have evaluated the efficacy of telbivudine in preventing intrauterine HBV infection during late pregnancy. So we conducted this meta-analysis to arrive at an evidence-based conclusion. We searched Medline/PubMed, EMBASE, Cochrane Library, Web of Knowledge and China Biological Medicine Database from January 1990 to December 2011. Relative risks (RR) of the seropositivity rates for hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants were studied. Mean differences (MD) in maternal HBV DNA levels were reviewed. Finally two randomised controlled trials (RCTs) and four non-randomised controlled trials (NRCTs) were left for analysis which included 576 mothers in total, of whom 306 received telbivudine treatment and 270 did not receive any drug. All newborns received hepatitis B vaccine (HBVac) and hepatitis B immunoglobulin (HBIG) after birth. The seropositivity rate for HBsAg or HBV DNA was significantly lower in the telbivudine group, both at birth and at 6--12 months follow up. Meanwhile, maternal HBV DNA levels prior to delivery were significantly lower in the telbivudine group. In addition, the frequency of serum creatine kinase (CK) elevation was similar in the two groups. Our meta-analysis provides preliminary evidence that telbivudine application in late pregnancy is effective in the interruption of intrauterine HBV infection, with no significant adverse effects or complications. More high quality, well-designed, double-blinded, randomised controlled and large size clinical trials are needed for further investigation and more convincing results in the future.     

Genetic effects of hydralazine.

Hydralazine and its acetone condensation product (ACP) were found to induce base-pair substitution mutations in the Salmonella/microsomal activation test system and to display genetic toxicity in the PolA+/A- test system. Incubation with a rat-liver microsomal fraction did not affect the genetic toxicity of either compound. Other derivatives of hydralazine, including the major metabolite, 3-hydroxy-methyl-s-triazolo-[3,4a]phthalazine, did not yield any evidence of genetic toxicity nor were they metabolically convertible to a toxic product. Therefore, individuals who convert hydralazine to MTP slowly, the "slow acetylators", would be expected to be at risk.     

Real-time measurements of acetylcholine-induced release of ATP from bovine medullary chromaffin cells

Long-term treatment with hydralazine is sometimes associated with deposition of immune complexes and development of systemic lupus erythematosus (SLE) as an adverse side-effect. Hydralazine inhibits the covalent binding reaction of the complement protein C4. We show that when hydralazine inhibits C4, it becomes covalently bound to the polypeptide chain containing the active site thiol ester. C4 is encoded at 2 adjacent polymorphic loci, C4A and C4B, within the major histocompatibility complex. We show that hydralazine binds more efficiently to the C4A than to the C4B gene product and suggest that C4 type may predispose patients to hydralazine-induced SLE.     

Effects of hydralazine on the blood flow in RIF-1 tumors and normal tissues of mice

Hydralazine is a peripheral vasodilator used as an antihypertensive agent. Hydralazine has been reported to potentiate tumor damage by hyperthermia as well as by hypoxic-cell-specific drugs through the reduction of tumor blood flow and pO2. In the present study, we investigated the changes in blood perfusion caused by hydralazine in S.C. RIF-1 tumors and normal tissues in C3H mice using the 86Rb uptake technique and laser Doppler flowmetry. The tumor blood flow was decreased significantly by an intravenous administration of 0.5-10.0 mg/kg hydralazine, as determined by both uptake of 86Rb and laser Doppler flowmetry. The tumor pO2 was also decreased significantly by the injection of hydralazine. On the other hand, the uptake of 86Rb was increased significantly in the skin and muscle by hydralazine. The changes seen in the skin and muscle after injection of hydralazine as assessed by laser Doppler flowmetry were similar to those assessed by uptake of 86Rb, indicating a significant increase in blood circulation in these tissues. Uptake of 86Rb remained unchanged in the kidney and decreased in the liver and spleen in the presence of hydralazine in a dose-dependent manner at 0.5-10.0 mg/kg. The decline in uptake of 86Rb in normal tissues strongly suggests that hydralazine decreases the blood flow in these normal tissues. Thus the recent proposal to use hydralazine to increase the antitumor activity of heat or certain drugs needs to be reexamined.