Acute lung injury is an inflammatory syndrome that increases the permeability of the blood-gas barrier, resulting in high morbidity and mortality. Despite intensive research, treatment options remain limited. We investigated the protective efficacy of
tezosentan, a novel, dual
endothelin receptor antagonist, in an experimental model of
alpha-naphthylthiourea (
ANTU)-induced
acute lung injury in rats.
ANTU was intraperitoneally (i.p.) injected into rats at a dose of 10 mg/kg.
Tezosentan was injected 30 minutes before
ANTU was subcutaneously (s.c.) injected at doses of 2, 10, or 30 mg/kg, 60 minutes before
ANTU was injected at doses of 2, 10, or 30 mg/kg (i.p.), and 90 minutes before
ANTU at a dose of 10 mg/kg (i.p.). Four hours later, the lung
weight/body weight (LW/BW) ratio and
pleural effusion (PE) were measured. When injected 30 minutes before
ANTU at doses of 2, 10, or 30 mg/kg (s.c.),
tezosentan had no effect on lung pathology. When injected 60 minutes before
ANTU at doses of 2, 10, or 30 mg/kg (i.p.) or 90 minutes before
ANTU (10 mg/kg, i.p.),
tezosentan significantly decreased the PE/BW ratio and had a prophylactic effect on PE formation at all doses. Therefore,
tezosentan may attenuate
lung injury. Furthermore, its acute and inhibitory effects on fluid accumulation were more effective in the pleural cavity than in the interstitial compartment in this experimental model.