Oxyhaemoglobin increases the production of endothelin-1 by endothelial cells in culture.
Cultured endothelial cells from bovine thoracic aortas conditioned with serum-free culture media released an endothelin-1 (ET)-1-like substance. Concentrations of ET-1-like material were determined by bioassay as contractions of isolated ring segments of dog internal mammary vein and by radioimmunoassay. ET-1-like immunoreactivity (ET-1-IR) increased progressively over a 24 h conditioning period and correlated with the bioassay for the first 12 h. Oxyhaemoglobin (1-3 microM) caused a significant two-fold increase in the concentration of ET-1-IR in the medium at 6, 8 and 12 h incubation. Methaemoglobin also caused an approximate doubling of the amount of ET-1-IR at eight h of incubation. NG-Monomethyl-L-arginine (L-NMMA), a blocker of the production of endothelium-derived relaxing factor (EDRF), had no effect on the time-dependent increase in ET-1-IR in the conditioned medium. These results may have important implications for the mechanisms underlying vascular smooth muscle hyperreactivity such as cerebral spasm following subarachnoid haemorrhage.
Cocks
T M
TM
Baker Medical Research Institute, Prahran, Victoria, Australia.
Malta
E
E
King
S J
SJ
Woods
R L
RL
Angus
J A
JA
D000818:Animals; D001681:Biological Assay; D002478:Cells, Cultured; D016232:Endothelins / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D010108:Oxyhemoglobins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010108:Oxyhemoglobins