Plasma nitric oxide, endothelin-1 and urinary nitric oxide and cyclic guanosine monophosphate levels in hypertensive pregnant women

Baksu, Başak; Davas, İnci; Baksu, Alparslan; Akyol, Atıf; Gülbaba, Günay

doi:10.1016/j.ijgo.2005.04.018

Cited by 59 publications

(39 citation statements)

References 24 publications

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“…Moreover, WT sFlt-1 mice treated with ET-1 develop renal phenotypes similar to eNOS 2/2 sFlt-1 mice, evidenced by more severe albuminuria, decreased CCr, severe endotheliosis, and foot process effacement (Supplemental Figures S1 and S2). Our results are consistent with studies showing the association of ET-1 with pre-eclampsia [17][18][19] and with a recent study showing that sFlt-1 increases ET-1 expression in glomerular endothelial cells, 26 that ET-1 binds to its receptor in podocytes and causes nephrin shedding and proteinuria, and that an ET A receptor antagonist N-acetyl-[D-TRP 16 ]-ET1 fragment 16-21 abolishes these serial effects. 26 Taken together, our results indicate that the activated ET system is responsible for pre-eclampsia-like phenotypes observed in WT sFlt-1 and eNOS 2/2 sFlt-1 mice.…”

Section: Discussionsupporting

confidence: 92%

“…ET-1 is one of the most potent vasoconstrictors and is associated with pre-eclampsia. [17][18][19] sFlt-1 and lack of eNOS both increase the expression of preproET-1 and ET A R in the kidney, and eNOS 2/2 sFlt-1 mice have the highest expression of these (Figure 4). A selective ET A R antagonist ambrisentan abolished about two-thirds of elevated BP by sFlt-1 in both WT and eNOS 2/2 mice, indicating that ET plays a major role in increases in BP of pre-eclampsia ( Figure 5A), but that the difference in BP between WT and eNOS 2/2 mice is ET independent.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Because NO inhibits ET-1 expression, 20,21 this suggests that decreased eNOS/NO might exacerbate pre-eclampsia by upregulating ET-1. To test this, we first determined the level of preproET-1 mRNA expression in the kidneys, which did not differ in mice with Ad Fc virus ( Figure 4A).…”

Section: Upregulation Of Preproet-1 and Et A Receptor In Enosmentioning

confidence: 99%

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eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype

Hagaman

Kim

et al. 2012

Journal of the American Society of Nephrology

109

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Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia-like features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsia-like phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (467674 versus 174623 mg/d), lower creatinine clearance (126629 versus 452663 ml/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ET A receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ET A receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsia-like phenotype through activation of the endothelin system. Pre-eclampsia is a pregnancy-related disease characterized by high BP and proteinuria, and affects 3%-5% of all pregnancies. 1,2 Although the etiology of pre-eclampsia is not fully understood, it is widely accepted that placental hypoxia/ischemia increases the production by the placenta of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin, and likely other factors. 1 Increased sFlt-1 is recognized as one of the most important causal factors for maternal symptoms of pre-eclampsia. 1 sFlt-1 is a splice variant of vascular endothelial growth factor (VEGF) receptor-1 that lacks the cytoplasmic and transmembrane domains, but retains the ligandbinding domain. sFlt-1 decreases the chance of VEGF binding to its signaling receptor, and reduces the phosphorylation of Ser 1177 of endothelial nitric oxide synthase (eNOS) by VEGF and the activity of eNOS. 3 Plasma concentration of sFlt-1 is

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype

Hagaman

Kim

et al. 2012

Journal of the American Society of Nephrology

109

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“…A previous study suggested that ET-1 plays an essential role in the failure of trophoblast invasion in the early stages of preeclampsia (12). Another study indicated that the level of circulating ET-1 correlates with the severity of the disease symptoms (4). Coincidental with the increase in circulating ET-1, Nishikawa et al reported a significant negative correlation between ET-1 levels and levels of the vasodilators NO and cGMP in preeclamptic women (24).…”

Section: Discussionmentioning

confidence: 98%

The effect of high altitude on endothelial and vascular dysfunction markers in preeclamptic patients

So¹,

Suekit²,

Ao³

et al. 2015

Acta Physiologica Hungarica

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Placental hypoxia, a major component of the pathophysiology of preeclampsia, is associated with various maternal vascular and endothelial dysfunctions. The higher incidence of preeclampsia at high altitude remains incompletely explained. The aim of the present study was to investigate the effect of high altitude on some endothelial and vascular dysfunction markers in normal and preeclamptic pregnancies. Eighty pregnant women (Paras 2-4) were enrolled in this study, which included four groups (each n = 20): normal pregnancies at low altitude (NL), normal pregnancies at high altitude (NH), preeclamptic pregnancies at low altitude (PL), and preeclamptic pregnancies at high altitude (PH). In normal pregnancies at high altitude serum ET-1, plasma TXA 2 , and serum TNF-α levels increased significantly with a significant reduction in plasma PGI 2 (66.81 ± 7.36, 122.86 ± 13.37, 102.23 ± 13.31, 191.57 ± 19.68, respectively) compared with the NL group (48.92 ± 4.58, 89.03 ± 10.67, 69.86 ± 7.97, 238.01 ± 24.55, respectively). In preeclampsia at low altitude serum ET-1, plasma TXA 2 , and serum TNF-α levels increased significantly with a significant reduction in plasma PGI 2 (88.39 ± 9.54, 162.73 ± 15.92, 142.39 ± 15.37, 149.155 ± 15.66, respectively) compared with both NL and NH groups. High altitude significantly augmented these changes in preeclamptic patients (117.75 ± 12.96, 211.01 ± 22.69, 196.86 ± 17.64, 111.92 ± 10.74) compared with PL, NH and NL groups. In conclusion hypoxia at high altitude aggravated the disturbances in the levels of ET-1, TXA 2 , PGI 2 and TNF-α associated with preeclampsia. This may contribute to the higher risk of preeclampsia at high altitude.

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“…In literature, a large number of studies describing changes in endothelial function markers in PE can be found, in particular, an increase of plasma endothelin-1 (Baksu et al, 2005a;Bernardi et al, 2008a), soluble vascular cell adhesion molecule (sVCAM), plasma fibronectin (Aydin et al, 2006;Dane et al, 2009) and tissue fibronectin (Powers et al, 2008), a decrease of plasma and urinary nitric oxide (NO) levels (Baksu et al, 2005a;Mao et al, 2009).…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Umbilical Cord Blood Changes in Neonates from a Preeclamptic Pregnancy

Catarino¹,

Rebelo²,

Belo³

et al. 2012

From Preconception to Postpartum

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Plasma nitric oxide, endothelin-1 and urinary nitric oxide and cyclic guanosine monophosphate levels in hypertensive pregnant women

Abstract: The imbalance between NO and ET-1 may play a significant role in the pathophysiology of preeclampsia.

Cited by 59 publications

References 24 publications

eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype

eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype

The effect of high altitude on endothelial and vascular dysfunction markers in preeclamptic patients

Umbilical Cord Blood Changes in Neonates from a Preeclamptic Pregnancy

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