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.