Effects of Sepiapterin Supplementation and NOS Inhibition on Glucocorticoid-Induced Hypertension

Thida, Mya; Earl, John; Zhao, Yan; Wang, Shuaian; Tse, C.S.; Vickers, Janine J; Sutton, Matthew; Ong, Sharon L.H.; Mori, Trevor A.; Croft, Kevin D.; Whitworth, Judith A.; Zhang, Yi

doi:10.1038/ajh.2010.27

Cited by 12 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We measured SBP values using a noninvasive automatic blood pressure analyser (NIPREM 564, Cibertec, Madrid, Spain) attached to the tail of rats after previously dilating vessels with a stove (36-37°C) for 5 minutes, as described elsewhere. 11,[32][33][34] The mean of five readings from each animal was considered to be the individual SBP value. Measurements were taken on gestational days E0, E7, E10 and E17 from 12 randomised rats per group.…”

Section: Systolic Blood Pressure (Sbp)mentioning

confidence: 99%

Sildenafil citrate improves perinatal outcome in fetuses from pre‐eclamptic rats

Herraiz

Pellicer

Serra

et al. 2012

BJOG

View full text Add to dashboard Cite

Objective To evaluate perinatal outcome after sildenafil citrate (SC) administration at the onset of pregnancy in a rat preeclampsia model.Design In vivo animal experimental study.Setting Fundació n IVI-Instituto Universitario IVI, Valencia, Spain.SampleControl and pre-eclampsia-induced pregnant Wistar rats exposed to chronic SC administration.Methods We evaluated the use of SC, which was tested as a potential therapeutic tool to maintain vasodilatation in complicated pregnancies. We have demonstrated previously that SC shows a hypotensive selective effect in normal rat pregnancies when compared with nonpregnant animals.Main outcome measures Maternal blood pressure, weight and mortality during pre-and postnatal development, maternal blood cellularity and haemodynamic changes with maternal and fetal Doppler quantitative indices.Results SC restores normal values of blood pressure, cell count and proteinuria for maternal syndrome. In offspring, SC improves weight gain and increases survival rates without fetotoxic effects. According to the haemodynamic results, SC has a significant effect on the resistance index in the uterine artery in pre-eclamptic animals, as it restores normal values to correlate with an increase in fetal perfusion through the ductus venosus.Conclusions These results suggest that SC administration during pregnancy may have a potential benefit for the treatment of hypertension during pregnancy by reversing the maternal effects of pre-eclampsia and by improving uteroplacental and fetal perfusion.

show abstract

Section: Systolic Blood Pressure (Sbp)mentioning

confidence: 99%

Sildenafil citrate improves perinatal outcome in fetuses from pre‐eclamptic rats

Herraiz

Pellicer

Serra

et al. 2012

BJOG

View full text Add to dashboard Cite

show abstract

“…Furthermore, administration of external BH 4 led to an increase of NO levels following GC-treatment, as it was demonstrated in animal studies as well as in coronal endothelial cells [51,54]. However, BH 4 application or treatment with sepiapterin, a precursor of BH 4 , did not alter systolic blood pressure although total concentrations of plasma BH 4 were elevated in GC-induced hypertensive rats [55,56]. GC effects on BH 4 and NO down-regulation have been proven to be genomic by the usage of specific GR antagonists.…”

Section: Effects On L-arginine and Bhmentioning

confidence: 85%

“…While sepiapterin is absorbed by cells and converted to intracellular BH 4 , a direct BH 4 administration acts extracellularly [43]. Despite this seemingly important difference, there is only one report describing sepiapterin administration, whereas a direct BH 4 administration has not been described in the context of GC-induced hypertension [56]. The low number of experimental data might be due to the fact that sepiapterin did not affect dexamethasone-mediated hypertension in rats although plasma levels of BH 4 were significantly increased.…”

Section: Bh 4 Supplementationmentioning

confidence: 93%

See 1 more Smart Citation

Role of Endothelial Nitric Oxide Synthase in Glucocorticoid- Induced Hypertension: An Overview of Experimental Data

Blecharz-Lang¹,

Burek²

2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

View full text Add to dashboard Cite

Imbalances in the synthesis or in the bioavailability of nitric oxide (NO), the freely diffusible vasodilator, in myocardial endothelial cells were demonstrated to be crucial in the development of hypertension. Glucocorticoids (GCs) are widely used as immunomodulators. One of the numerous side effects of GC therapy is hypertension arising from reduced release of the endothelium-derived NO. GCs can modulate NO synthesis by targeting the genes involved in it, like nitric oxide synthase (NOS) and guanosine triphosphate (GTP) cyclohydrolase-1 (GTPCH-1). This chapter will give an overview on the impact of GCs on NO synthesis and signalling in animal models as well as in in vitro cell culture models. Moreover, strategies for preventing or neutralizing side effects of long-term GC therapy will be discussed.

show abstract

“…While we chose to focus on SLE in this study, diabetic and hypertensive renal disease are also known to be associated with endothelial dysfunction that improves with therapy targeting eNOS dysfunction. [49][50][51] This study established that factors in the serum of patients with lupus and LN induce an endothelial cell inflammatory phenotype in renal glomerular endothelial cells, which is manifested by neutrophil adhesion and migration. It also demonstrates the effect of disease activity on this phenotype using paired visit serum samples from individual patients during inactive and active disease states.…”

Section: Immunology and Inflammationmentioning

confidence: 91%

Lupus serum induces inflammatory interaction with neutrophils in human glomerular endothelial cells

2020

View full text Add to dashboard Cite

ObjectivesSLE is associated with endothelial cell dysfunction (ECD). Understanding how ECD leads to neutrophil infiltration into glomeruli is essential to finding therapeutic targets for SLE. The aim of this study is to determine the effect of SLE serum from patients with active disease to induce neutrophil adhesion to and chemotaxis towards glomerular endothelial cells and factors induced by serum that associate with neutrophil chemotaxis.MethodsPatients with SLE had serum collected during paired longitudinal visits with lower and higher activity. 13 patients with SLE (5 SLE, 5 SLE with hypertension (HTN) and 3 SLE lupus nephritis (LN) and HTN), and 10 healthy controls (5 with and 5 without HTN) were examined. The adhesion of neutrophils to serum-treated human renal glomerular endothelial cells (HRGECs) or chemotaxis of neutrophils towards conditioned media from serum-treated HRGECs was determined, and levels of cytokines in this conditioned medium were quantified. Pathway analysis of cytokines induced by SLE and LN serum that associated with neutrophil migration was performed.ResultsHRGECs treated with SLE serum induced significantly greater neutrophil chemotaxis and adhesion compared with control serum. When examining specific cohorts, SLE HTN and LN HTN promoted greater neutrophil chemotaxis than control serum, while SLE HTN and LN HTN promoted greater chemotaxis than SLE serum. Serum from active disease visits promoted neutrophil chemotaxis and adhesion over paired inactive visits. Levels of platelet-derived growth factor-BB, interleukin (IL)-15 and IL-8 secreted by SLE serum-treated HRGECs positively correlated with neutrophil chemotaxis. Pathway analysis suggested that LN serum induced pathways important in endoplasmic reticulum and oxidative stress.ConclusionsSLE serum induces expression of mediators by HRGECs that promote neutrophil chemotaxis and adhesion, which increases during disease activity, and associates with factors common to pathways of endoplasmic reticulum and oxidative stress. These findings highlight the potential importance of serum factor-induced ECD in SLE and LN.

show abstract

Effects of Sepiapterin Supplementation and NOS Inhibition on Glucocorticoid-Induced Hypertension

Abstract: Sepiapterin did not prevent ACTH- or dexamethasone-induced hypertension. NOLA exacerbated dexamethasone-induced hypertension. These data suggest that eNOS uncoupling does not play a major role in the genesis of glucocorticoid-induced hypertension in the rat.

Cited by 12 publications

References 33 publications

Sildenafil citrate improves perinatal outcome in fetuses from pre‐eclamptic rats

Sildenafil citrate improves perinatal outcome in fetuses from pre‐eclamptic rats

Role of Endothelial Nitric Oxide Synthase in Glucocorticoid- Induced Hypertension: An Overview of Experimental Data

Lupus serum induces inflammatory interaction with neutrophils in human glomerular endothelial cells

Contact Info

Product

Resources

About