title: Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Life Science Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Japan. t-miyauc@md.tsukuba.ac.jp
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakai
authors.forename: Seiji
authors.initials: S
authors.lastname: Maeda
authors.forename: Nobutake
authors.initials: N
authors.lastname: Shimojo
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Honma
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuga
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aonuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood*; D019333:Endothelin-2 / Q000097:blood*; D019334:Endothelin-3 / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D006435:Renal Dialysis
chemical_list: D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D011498:Protein Precursors; C406477:big endothelin 2