Tezosentan is a novel dual
endothelin receptor antagonist. The purpose of this study was to examine the effect of
tezosentan on
lung injury induced by abdominal aortic
ischemia-reperfusion (IR) in rats. Thirty-two Wistar-albino rats were randomized into four groups (eight per group) as follows: control group (
sham laparotomy), aortic IR group (120 min
ischemia and 120 min reperfusion), aortic IR +
tezosentan group (a bolus
intravenous injection of 10 mg/kg
tezosentan before
ischemia plus continuous
intravenous infusion of 1 mg/kg/hr
tezosentan during 120 min
ischemia and 120 min reperfusion), and control +
tezosentan. Blood and lung tissue samples were obtained for biochemical analysis.
Protein concentrations in bronchoalveolar lavage fluid and
lung wet/dry weight ratios were measured. A histological evaluation was also done. Aortic IR significantly increased (p < 0.05 vs. control group) and
tezosentan significantly decreased (p < 0.05 vs. aortic IR group) the plasma level of
tumor necrosis factor-alpha; lung tissue levels of
malondialdehyde,
catalase, and myleperoxidase; and
protein concentration in bronchoalveolar lavage fluid and
lung wet/dry weight ratio. Histological evaluation showed that
tezosentan attenuated the morphological changes associated with
lung injury. The results of this study indicate that
tezosentan attenuates
lung injury induced by aortic IR in rats. We propose that this protective effect of
tezosentan is due to (1) reduced systemic inflammatory response, (2) reduced oxidative stress and lipid peroxidation in lung tissue, (3) reduced pulmonary microvascular leakage, and (4) inhibition of leukocyte infiltration into lung tissue.