Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease

Yumi Miyauchi, Satoshi Sakai, Seiji Maeda, Nobutake Shimojo, Shigeyuki Watanabe, Satoshi Honma, Keisuke Kuga, Kazutaka Aonuma, Takashi Miyauchi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Aims: Big endothelins (pro-endothelin; inactive-precursor) are converted to biologically active endothelins (ETs). Mammals and humans produce three ET family members: ET-1, ET-2 and ET-3, from three different genes. Although ET-1 is produced by vascular endothelial cells, these cells do not produce ET-3, which is produced by neuronal cells and organs such as the thyroid, salivary gland and the kidney. In patients with end-stage renal disease, abnormal vascular endothelial cell function and elevated plasma ET-1 and big ET-1 levels have been reported. It is unknown whether big ET-2 and big ET-3 plasma levels are altered in these patients. The purpose of the present study was to determine whether endogenous ET-1, ET-2, and ET-3 systems including big ETs are altered in patients with end-stage renal disease. Main methods: We measured plasma levels of ET-1, ET-3 and big ET-1, big ET-2, and big ET-3 in patients on chronic hemodialysis (n = 23) and age-matched healthy subjects (n = 17). Key findings: In patients on hemodialysis, plasma levels (measured just before hemodialysis) of both ET-1 and ET-3 and big ET-1, big ET-2, and big ET-3 were markedly elevated, and the increase was higher for big ETs (Big ET-1, 4-fold; big ET-2, 6-fold; big ET-3: 5-fold) than for ETs (ET-1, 1.7-fold; ET-3, 2-fold). Significance: In hemodialysis patients, plasma levels of the inactive precursors big ET-1, big ET-2, and big ET-3 levels are markedly increased, yet there is only a moderate increase in plasma levels of the active products, ET-1 and ET-3. This suggests that the activity of endothelin converting enzyme contributing to circulating levels of ET-1 and ET-3 may be decreased in patients on chronic hemodialysis.

Original languageEnglish
Pages (from-to)729-732
Number of pages4
JournalLife Sciences
Issue number13-14
Publication statusPublished - 2012 Oct 15
Externally publishedYes


  • Big endothelin
  • Endothelin
  • Hemodialysis patients
  • Renal disease

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics(all)


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