Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease

S. Xiao, L. Wágner, R. J. Schmidt, C. Baylis

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Background. Chronic renal disease (CRD) is associated with hypertension and reduced synthesis of nitric oxide (NO). Here, we investigated whether there is a circulating endothelial NO synthase (eNOS) inhibitory factor(s) in some patients with CRD that might directly influence endothelial NOS. Methods. Human dermal microvascular endothelial cells (HDMECs) were incubated for six hours with 20% plasma from subjects with normal renal function (PCr = 0.8 ± 0.2 mg%), and patients with moderate renal insufficiency of various causes (PCr = 4.0 ± 1.5 mg%) and impact on NOS activity, transport of L-arginine, and abundance of eNOS protein were measured. Plasma concentrations of asymmetric and symmetric dimethyl L-arginine (ADMA and SDMA) were also measured. Results. There was no effect of any human plasma on L-arginine transport. The NOS activity was variable in CRD patients and fell into two subgroups: CRD I, individual values similar to control, and CRD II, individual values lower than control mean. The effect of CRD plasma on NOS activity in cultured cells was not related to the primary disease, but was predicted by plasma ADMA levels since plasma ADMA was elevated in CRD II versus both control and CRD I. Blood urea nitrogen and creatinine levels were uniformly elevated in CRD plasma. The abundance of eNOS protein was unaffected by plasma. Conclusion. High plasma levels of ADMA in CRD patients are independent of reduced renal clearance, suggesting an alteration in ADMA synthesis and/or degradation. High ADMA is a marker and is partly responsible for the inhibition of eNOS activity in cultured cells and may also result in reduced eNOS activity in vivo, with consequent hypertension.

Original languageEnglish
Pages (from-to)1466-1472
Number of pages7
JournalKidney International
Volume59
Issue number4
DOIs
Publication statusPublished - 2001

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Nitric Oxide Synthase Type III
Chronic Renal Insufficiency
Nitric Oxide Synthase
Arginine
Cultured Cells
Hypertension
Kidney
Blood Urea Nitrogen
Renal Insufficiency
Creatinine
Nitric Oxide
Proteins
Endothelial Cells
Skin

Keywords

  • Asymetric dimethylarginine
  • Cell culture
  • End-stage renal disease
  • Human dermal microvascular endothelial cells
  • L-arginine transport

ASJC Scopus subject areas

  • Nephrology

Cite this

Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease. / Xiao, S.; Wágner, L.; Schmidt, R. J.; Baylis, C.

In: Kidney International, Vol. 59, No. 4, 2001, p. 1466-1472.

Research output: Contribution to journalArticle

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abstract = "Background. Chronic renal disease (CRD) is associated with hypertension and reduced synthesis of nitric oxide (NO). Here, we investigated whether there is a circulating endothelial NO synthase (eNOS) inhibitory factor(s) in some patients with CRD that might directly influence endothelial NOS. Methods. Human dermal microvascular endothelial cells (HDMECs) were incubated for six hours with 20{\%} plasma from subjects with normal renal function (PCr = 0.8 ± 0.2 mg{\%}), and patients with moderate renal insufficiency of various causes (PCr = 4.0 ± 1.5 mg{\%}) and impact on NOS activity, transport of L-arginine, and abundance of eNOS protein were measured. Plasma concentrations of asymmetric and symmetric dimethyl L-arginine (ADMA and SDMA) were also measured. Results. There was no effect of any human plasma on L-arginine transport. The NOS activity was variable in CRD patients and fell into two subgroups: CRD I, individual values similar to control, and CRD II, individual values lower than control mean. The effect of CRD plasma on NOS activity in cultured cells was not related to the primary disease, but was predicted by plasma ADMA levels since plasma ADMA was elevated in CRD II versus both control and CRD I. Blood urea nitrogen and creatinine levels were uniformly elevated in CRD plasma. The abundance of eNOS protein was unaffected by plasma. Conclusion. High plasma levels of ADMA in CRD patients are independent of reduced renal clearance, suggesting an alteration in ADMA synthesis and/or degradation. High ADMA is a marker and is partly responsible for the inhibition of eNOS activity in cultured cells and may also result in reduced eNOS activity in vivo, with consequent hypertension.",
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N2 - Background. Chronic renal disease (CRD) is associated with hypertension and reduced synthesis of nitric oxide (NO). Here, we investigated whether there is a circulating endothelial NO synthase (eNOS) inhibitory factor(s) in some patients with CRD that might directly influence endothelial NOS. Methods. Human dermal microvascular endothelial cells (HDMECs) were incubated for six hours with 20% plasma from subjects with normal renal function (PCr = 0.8 ± 0.2 mg%), and patients with moderate renal insufficiency of various causes (PCr = 4.0 ± 1.5 mg%) and impact on NOS activity, transport of L-arginine, and abundance of eNOS protein were measured. Plasma concentrations of asymmetric and symmetric dimethyl L-arginine (ADMA and SDMA) were also measured. Results. There was no effect of any human plasma on L-arginine transport. The NOS activity was variable in CRD patients and fell into two subgroups: CRD I, individual values similar to control, and CRD II, individual values lower than control mean. The effect of CRD plasma on NOS activity in cultured cells was not related to the primary disease, but was predicted by plasma ADMA levels since plasma ADMA was elevated in CRD II versus both control and CRD I. Blood urea nitrogen and creatinine levels were uniformly elevated in CRD plasma. The abundance of eNOS protein was unaffected by plasma. Conclusion. High plasma levels of ADMA in CRD patients are independent of reduced renal clearance, suggesting an alteration in ADMA synthesis and/or degradation. High ADMA is a marker and is partly responsible for the inhibition of eNOS activity in cultured cells and may also result in reduced eNOS activity in vivo, with consequent hypertension.

AB - Background. Chronic renal disease (CRD) is associated with hypertension and reduced synthesis of nitric oxide (NO). Here, we investigated whether there is a circulating endothelial NO synthase (eNOS) inhibitory factor(s) in some patients with CRD that might directly influence endothelial NOS. Methods. Human dermal microvascular endothelial cells (HDMECs) were incubated for six hours with 20% plasma from subjects with normal renal function (PCr = 0.8 ± 0.2 mg%), and patients with moderate renal insufficiency of various causes (PCr = 4.0 ± 1.5 mg%) and impact on NOS activity, transport of L-arginine, and abundance of eNOS protein were measured. Plasma concentrations of asymmetric and symmetric dimethyl L-arginine (ADMA and SDMA) were also measured. Results. There was no effect of any human plasma on L-arginine transport. The NOS activity was variable in CRD patients and fell into two subgroups: CRD I, individual values similar to control, and CRD II, individual values lower than control mean. The effect of CRD plasma on NOS activity in cultured cells was not related to the primary disease, but was predicted by plasma ADMA levels since plasma ADMA was elevated in CRD II versus both control and CRD I. Blood urea nitrogen and creatinine levels were uniformly elevated in CRD plasma. The abundance of eNOS protein was unaffected by plasma. Conclusion. High plasma levels of ADMA in CRD patients are independent of reduced renal clearance, suggesting an alteration in ADMA synthesis and/or degradation. High ADMA is a marker and is partly responsible for the inhibition of eNOS activity in cultured cells and may also result in reduced eNOS activity in vivo, with consequent hypertension.

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