Evaluation of nitric oxide as a mediator of severe preeclampsia

Silver, Richard K.; Kupferminc, Michael J.; Russell, Tanya L.; Adler, Luba; Mullen, Tiffany A; Caplan, Michael S.

doi:10.1016/s0002-9378(96)80044-5

Cited by 79 publications

(32 citation statements)

References 19 publications

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“…16 Several studies have measured circulating NO levels in PE and found them to be decreased, 17 increased 5,18 or unchanged. 19 We did not find any significant differences in the total circulating NO levels in any of the groups. However, this endothelium-derived molecule has a short half-life and largely acts in an autocrine or paracrine manner, hence circulating levels may not truly reflect the local NO concentration and/or activity.…”

Section: Discussionmentioning

confidence: 49%

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

2010

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We investigated the variations in genes encoding endothelial nitric oxide synthase (NOS3), angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) in hypertensive disorders of pregnancy and the relationship between the polymorphisms and circulating nitric oxide (NO) and ACE levels in pregnant north Indian women. Frequencies of NOS3 G894T, 4b/a and T -786 -C, AGT T704C and ACE ins/del polymorphisms were studied in 342 subjects: 120 with preeclampsia (PE), 104 with gestational hypertension and 118 normotensive pregnant women. Variations were evaluated by polymerase chain reactionrestriction fragment length polymorphism. NO and ACE levels were determined using ELISA. There was no difference in the distribution of individual NOS3 and ACE polymorphisms in the study groups. Haplotype analysis showed a global difference in the NOS3 haplotype distribution between the PE and non-PE subjects (P¼0.03). The presence of AGT 704C allele was associated with a reduced risk of developing PE (odds ratio: 0.33, 95% CI: 0.19-0.59 in recessive mode). Circulating total NO and ACE levels were similar in three groups. No relationship was found between circulating NO levels and any of the NOS3 polymorphisms, but the circulating ACE levels were higher in those with DD genotype (Po0.05). In conclusion, there was no association between individual NOS3 and the ACE gene polymorphisms and hypertensive disorders of pregnancy in north Indian women. The presence of minor alleles at all the three sites in NOS3 seemed to increase the risk of PE, and AGT 704C allele was associated with a reduced PE risk. The complexity of interaction between these genetic abnormalities requires further studies.

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Section: Discussionmentioning

confidence: 49%

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

2010

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“…Some studies have shown a decreased nitric oxide production in preeclampsia whereas other studies have shown conflicting results. [14][15][16] Cockell et al 17 reported flowmediated dilation in the subcutaneous artery to be impaired in pre-eclampsia, thus suggesting the existence of endothelial dysfunction in pre-eclampsia. The earlier report 18 has suggested that an abnormality in the resistance-artery endothelium may be present in patients with pre-eclampsia.…”

Section: Discussionmentioning

confidence: 99%

Flow-mediated dilation in brachial artery in the second half of pregnancy and prediction of pre-eclampsia

et al. 2003

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Endothelial injury and increased vascular reactivity are involved in the pathogenesis of pre-eclampsia (pregnancy-induced hypertension). To investigate whether flow-mediated dilation (endothelium-dependent dilation) and the reactive hyperemic response can predict preeclampsia, we prospectively measured flow-mediated dilation and the Doppler flow velocity pattern (V, cm/s) in the brachial artery using high-resolution ultrasound in 43 pregnant women (32 7 5 years old) in the second half of their pregnancy, and compared the findings with traditional risk factors. Regarding the Doppler flow velocity pattern, the pulsatility index (PI) ¼ (systolic VÀdiastolic V)/mean V and resistance index (RI) ¼ (systolic VÀdiastolic V)/systolic V were calculated. For the flow-mediated dilation, the per cent diameter changes were determined based on those from baseline to hyperemic conditions. Nine women suffered from preeclampsia and 34 women remained normotensive. Only flow-mediated dilation was found to be significantly lower in the subsequently developed pre-eclampsia patients (1.6 7 1.0% in subsequently developed preeclampsia patients vs 11.0 7 4.5% in normotensive patients, Po0.05). Neither the other traditional factors nor the Doppler flow velocity pattern were significantly different between the subsequently developed preeclampsia and normotensive patients. If a normal cutoff value of 3.0% obtained from age-matched 14 nonpregnant women (32 7 7 years old) in our laboratory was used, the positive predictive value of flow-mediated dilation (o3.0%) for subsequent pre-eclampsia is 90% and the negative predictive value is 100%. In conclusion, flow-mediated dilation in brachial artery can be a simple and noninvasive modality to predict pre-eclampsia.

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“…Seligman et al [18] reported that circulating levels of nitrite are decreased in patients with preeclampsia. However, some authors [19][20][21] showed that there is no significant difference of plasma concentrations of nitrate and nitrite between women with preeclampsia and women with normal pregnancies. Recent studies [11,22] suggested that the plasma concentrations of nitrate and nitrite in patients with preeclampsia are higher than those in the normotensive women.…”

Section: Discussionmentioning

confidence: 99%

Maternal Circulating Nitrite Levels Are Decreased in both Normal Normotensive Pregnancies and Pregnancies with Preeclampsia

Hata

Hashimoto

Kanenishi

et al. 1999

Gynecol Obstet Invest

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Objective: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. Materials: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks’ gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. Results: Maternal circulating nitrite levels in nonpregnant women (1.13 ± 0.22 μM) were significantly higher than those in the first-trimester pregnant women (0.68 ± 0.13 μM), second-trimester pregnant women (0.65 ± 0.13 μM), third-trimester pregnant women (0.48 ± 0.17 μM), first puerperal week women (0.36 ± 0.16 μM), and fourth puerperal week women (0.67 ± 0.17 μM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 ± 0.17 μM) and third-trimester pregnant women (0.48 ± 0.17 μM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the gorups. Conclusion: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

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Evaluation of nitric oxide as a mediator of severe preeclampsia

Cited by 79 publications

References 19 publications

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

Endothelial nitric oxide synthase, angiotensin-converting enzyme and angiotensinogen gene polymorphisms in hypertensive disorders of pregnancy

Flow-mediated dilation in brachial artery in the second half of pregnancy and prediction of pre-eclampsia

Maternal Circulating Nitrite Levels Are Decreased in both Normal Normotensive Pregnancies and Pregnancies with Preeclampsia

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