Immunohistochemical characterization of placental nitric oxide synthase expression in preeclampsia

doi:10.1016/0002-9378(95)90324-0

American Journal of Obstetrics and Gynecology

Volume 173, Issue 3, Part 1, September 1995, Pages 687-694

https://doi.org/10.1016/0002-9378(95)90324-0 Get rights and content

Abstract

OBJECTIVE: Our purpose was to compare the expression of endothelial nitric oxide synthase in the placenta and umbilical cord of preeclamptic placenta with that of the normotensive placenta.

STUDY DESIGN: We compared placental endothelial nitric oxide synthase expression in preeclamptic (n = 3) with that in normal (n = 3) pregnancies. Frozen sections of umbilical cords, chorionic plate vessels, and terminal villi were immunostained with a monoclonal endothelial nitric oxide synthase antibody (H32).

RESULTS: No difference in endothelial nitric oxide synthase immunostaining in the endothelium of the umbilical cord artery and vein, chorionic plate vessels, and stem villous vessels was found between preeclamptic and normotensive pregnancies. In contrast, in the preeclamptic placentas endothelial nitric oxide synthase immunostaining was seen in the small terminal villous vessels with underlying smooth muscle layer. In the syncytiotrophoblast endothelial nitric oxide synthase immunostaining appeared primarily apical in location and diffuse in distribution in the preeclamptic placentas but primarily basal and punctate in the normotensive placentas.

CONCLUSIONS: Differences in endothelial nitric oxide synthase expression in terminal villous vessels and in syncytiotrophoblast may be a result of vascular alterations or damage that take place in the placenta in preeclampsia. These differences may alter the regulation of blood flow in the fetal and maternal placental vasculatures in preeclampsia.

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The renin-angiotensin-aldosterone-system (RAAS) and nitric oxide (NO) system are two very critical pathways in regulating cell proliferation, endothelial function, angiogenesis, neuroendocrine systems, oxidative stress, and blood pressure. Functional imbalance of RAAS and/or NO plays an important pathogenetic role in vasoconstriction and vasodilation and can result in hypertensive end-organ injury. This chapter summarizes pathophysiological roles and disorders related to RAAS and NO, especially during the perinatal periods, including preeclampsia, gestational diabetes, intrauterine growth restriction, early embryo loss, preterm birth, neonatal pulmonary hypertension, kidney disorders, and primary hyper- and hypoaldosteronism. In the placenta, both angiotensin II and NO have special actions as compared with blood vessels in other organs, thereby contributing to the development of certain disorders during pregnancy.
Pathophysiological Roles and Disorders of Renin-Angiotensin-Aldosterone System and Nitric Oxide During Perinatal Periods
2019, Maternal-Fetal and Neonatal Endocrinology: Physiology, Pathophysiology, and Clinical Management
The renin-angiotensin-aldosterone-system (RAAS) and nitric oxide (NO) system are two very critical pathways in regulating cell proliferation, endothelial function, angiogenesis, neuroendocrine systems, oxidative stress, and blood pressure. Functional imbalance of RAAS and/or NO plays an important pathogenetic role in vasoconstriction and vasodilation and can result in hypertensive end-organ injury. This chapter summarizes pathophysiological roles and disorders related to RAAS and NO, especially during the perinatal periods, including preeclampsia, gestational diabetes, intrauterine growth restriction, early embryo loss, preterm birth, neonatal pulmonary hypertension, kidney disorders, and primary hyper- and hypoaldosteronism. In the placenta, both angiotensin II and NO have special actions as compared with blood vessels in other organs, thereby contributing to the development of certain disorders during pregnancy.
Differential regional fatty acid distribution in normotensive and preeclampsia placenta
2015, BBA Clinical
Citation Excerpt :
Recently we have shown increased levels of MDA and decreased levels of catalase an antioxidant enzyme in a region specific manner in the PE placenta [23]. Further, studies have also reported regionwise alterations in the inflammatory cytokines, nitric oxide synthase enzyme and heat shock proteins in the PE placenta [20,24–26]. It is likely that the LCPUFA metabolism may differ in the placenta depending upon the requirement by the trophoblast cells for different physiological processes.
Long chain polyunsaturated fatty acids (LCPUFAs) are biologically active fatty acids which regulate placental angiogenesis, inflammation, and oxidative stress. Abnormalities in these aspects have been associated with preeclampsia (PE). Further, placenta has a heterogeneous structure with differential vascularization across different regions. We therefore hypothesize that the distribution of fatty acids in various regions of the placenta is altered in PE leading to poor fetal outcome.
In this cross-sectional study we recruited 69 normotensive control (NC) and 44 women with PE. PE women were further classified as those delivered preterm (PTPE, n = 24) and at term (TPE, n = 20). Fatty acid levels were analyzed from placental samples from four different regions (CF—central fetal, PF—peripheral fetal, CM—central maternal and PM—peripheral maternal).
In the NC placenta, AA levels were lower (p < 0.05) in CM as compared with CF region. However, such differences were not seen in the TPE and PTPE. In contrast, the DHA levels varied between regions only in the PTPE placenta. Between groups, DHA levels were lower (p < 0.05 for both) in the CM and CF regions of the PTPE as compared with NC. The levels of DHA in TPE placenta were similar to NC. AA levels were lower (p < 0.05 for both) in CF region of TPE and PF region of PTPE placenta than NC.
There is differential pattern of LCPUFA distribution across various regions of the NC, TPE and PTPE placenta. This may have implications for placental growth and development as well as transfer of LCPUFA to the fetus.
Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia
2015, Placenta
Citation Excerpt :
As the placenta receives no autonomic input, it relies upon vasoactive mediators to regulate its vascular reactivity. Nitric oxide (NO) plays an integral role in controlling vascular resistance within the placenta; a disruption of this pathway has been identified in pre-eclampsia [1]. NO production is catalysed by the conversion of l-arginine to NO by NO synthases (NOS), two isoforms being present in the placenta: endothelial and inducible NOS (eNOS/iNOS) [2].
Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/iNOS in normotensive control (n = 24) and pre-eclamptic pregnancies (n = 19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P < 0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P = 0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation.
Is there a link between endothelial dysfunction, coagulation activation and nitric oxide synthesis in preeclampsia?
2013, Clinica Chimica Acta
Citation Excerpt :
In fact, NO synthesis in PE has been investigated by different methods but results were inconsistent. Thus, increased [24–27], decreased [28–32] or unchanged [33–37] NO synthesis in women with PE have been reported. Methodological shortcomings and sources of specimens may have contributed to such findings.
There may be a relationship between endothelial dysfunction, coagulation activation and nitric oxide (NO) synthesis in women with mild and severe preeclampsia (PE).
Plasma thrombomodulin (TM), D-Dimer (D-Di), cyclic guanosine monophosphate (cGMP) and placental nitric oxide synthase activity (NOS) were investigated in 21 normotensive pregnant women (G1), 22 pregnant women with mild PE (G2) and 20 pregnant women with severe PE (G3).
TM and D-Di were significantly increased in G3 compared to G1 (P = 0.001 and P = 0.006, respectively) and G2 (P = 0.001, in both cases). However, there was no significant difference when G1 was compared to G2. For total NOS, calcium independent NOS, calcium dependent NOS no significant difference was observed among the groups studied.
TM and D-Di levels are raised in women with severe PE compared to normotensive pregnant women and women with mild PE. While increased TM levels may reflect endothelial dysfunction, raised D-Di levels indicate a hypercoagulable state. NO assessed by 2 indirect methods did not show any significant difference among the groups studied. Due to current limitations with in vitro NO measurements and interferences associated with NO bioavailability, particularly in PE, such findings should not be over-interpreted.
Nitric oxide (NO) inhibits prostaglandin E2 9-ketoreductase (9-KPR) activity in human fetal membranes
2006, Prostaglandins and Other Lipid Mediators
Nitric oxide (NO) synthesized by fetal membranes may act either directly inhibiting myometrium contractility or indirectly interacting with tocolytic agents as prostaglandins (PGs). Here we examined if NO could modulate prostaglandin E₂ 9-ketoreductase (9-KPR) activity in human fetal membranes (HFM). 9-KPR is the enzyme that converts PGE₂ into PGF_2α, the main PGs known to induce uterine contractility at term. Chorioamnion explants obtained from elective caesareans were incubated with aminoguanidine (AG), an iNOS inhibitor, or NOC-18, a NO donor. NOC-18 (2 mM) increased PGE₂ production and diminished PGF_2α synthesis in HFM. AG presented the opposite effect. When we evaluated the activity of 9-KPR by the conversion of [³H]-PGE₂ into [³H]-PGF_2α and 13,14-dihidro-15-keto prostaglandin F_2α (the PGF_2α metabolite), we found that NOC-18 inhibited 9-KPR activity. Interestingly, AG did not elicit any effect on 9-KPR but l-NAME, a non-selective NOS inhibitor, significantly increased its activity. Our data suggests that exogenous NO inhibits 9-KPR activity in HFM, thus modulating the synthesis of important labor mediators as PGF_2α.

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^☆: Supported by National Institutes of Health grant No. HL 47860.

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General obstetrics and gynecologyImmunohistochemical characterization of placental nitric oxide synthase expression in preeclampsia☆

Abstract

Placenta

Lancet

FEBS Lett

Planceta

Planceta

Am J Obstet Gynecol

Am J Obstet Gynecol

Placenta

Placenta

Am J Obstet Gynecol

Pregnancy-related hypertension

Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia

Am J Hypertens

General obstetrics and gynecology
Immunohistochemical characterization of placental nitric oxide synthase expression in preeclampsia☆