Influence of endothelin 1 receptor blockers and a nitric oxide synthase inhibitor on reactive oxygen species formation in rat lungs.

UNLABELLED: This study was designated to estimate protective role of ETA and ETB receptor antagonist against endothelin 1 (ET-1)-induced oxidative stress in lungs and determine whether these effects are mediated by nitric oxide (NO) synthase. Experiments were performed on Wistar rats divided into the following groups: I - saline (0.9 % NaCl); II - ET-1 (3 microg/kg b.w.), III - BQ123 (1 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), IV - BQ788 (3 mg/kg b.w.) + ET-1 (3 microg/kg b.w.), V - N-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg b.w.) + ET-1 (3 microg/kg b.w.). ETA and ETB receptor antagonists or L-NAME were administered 30 min before ET-1 injection. The levels of the following substances were measured in the lungs homogenates: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-alpha). The results showed that ET-1 significantly increased TBARS, H(2)O(2) (respectively: p<0.001, p<0.02) and TNF-alpha levels (p<0.02) and decreased the GSH level (p<0.01) vs.

CONTROL GROUP: On the other hand, prior administration of ETA receptor blocker (BQ123) significantly attenuated TBARS (p<0.01), H(2)O(2) (p<0.02), TNF-alpha (p<0.02) and increased GSH (p<0.02) levels vs. ET-1. However, prior administration of ETB receptor blocker BQ788 did not cause significant changes in the: TBARS, H(2)O(2) and TNF-alpha (p>0.05) levels, but significantly increased the GSH level and GSH/GSSG ratio (p<0.05). Administration of L-NAME significantly attenuated TBARS (p<0.001), H(2)O(2) (p<0.05), TNF-alpha (p<0.01) and increased GSH (p<0.05) levels vs. ET-1. In conclusion, we demonstrated that ET-1 induced oxidative stress in the lungs is mediated by ETA receptors. ETA receptor blockage inhibited generation of free radicals and TNF-alpha and ameliorated antioxidant properties. Moreover, generation of reactive oxygen species is mediated by NOS in the lungs.