Carbon monoxide inhibits endothelin-1 release by human pulmonary artery smooth muscle cells.
Endothelin-1 is a potent vasoconstrictor with mitogenic properties. This 21-amino-acid protein, released in the vasculature by endothelial and smooth muscle cells, has been implicated in pulmonary hypertension. More recently, evidence has accumulated for a role of the heme oxygenase system in pulmonary hypertension. Heme oxygenase catalyses the breakdown of heme to produce carbon monoxide, biliverdin and free iron. Here we show that a carbon monoxide-releasing molecule, but not biliverdin, inhibits endothelin-1 release from serum-stimulated human pulmonary artery smooth muscle cells. Under certain conditions, carbon monoxide appears to act as an endogenous break on endothelin-1 release.
Unit of Critical Care, The Royal Brompton and Harefield NHS Trust, Imperial College School of Medicine, Sydney Street, London SW3 6NP, UK.
Salome J
SJ
Stanford
Matthew J
MJ
Walters
Jane A
JA
Mitchell
D001664:Biliverdine / Q000378:metabolism / Q000494:pharmacology; D002248:Carbon Monoxide / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D044967:Serum; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019332:Endothelin-1; D014409:Tumor Necrosis Factor-alpha; D002248:Carbon Monoxide; D007371:Interferon-gamma; D006419:Heme Oxygenase (Decyclizing); D001664:Biliverdine