Endothelin antagonists: new bullets against lung injury?

Acute lung injury is a syndrome of inflammation and of increased permeability of the blood-gas barrier. Endothelins are thought to exert proinflammatory effects. Kuklin and colleagues show that the endothelin receptor antagonist tezosentan reduces pulmonary edema in endotoxemic sheep, in parallel with a prevention of protein kinase C-alpha activation. In turn, the level of some cytokines increased after tezosentan treatment. Whether these contrasting effects of endothelin blockade on inflammatory mechanisms have clinical relevance and whether these agents might benefit patients with acute lung injury is unknown.