title: Influence of endothelin 1 receptor blockers and a nitric oxide synthase inhibitor on reactive oxygen species formation in rat lungs.
abstract: 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.
  
  
  
  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.
authors.affiliation: Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Lodz, Poland. paulina.kleniewska@umed.lodz.pl.
authors.forename: P
authors.initials: P
authors.lastname: Kleniewska
authors.forename: A
authors.initials: A
authors.lastname: Gorąca
mesh_terms: D000818:Animals; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D019332:Endothelin-1; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017382:Reactive Oxygen Species; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014409:Tumor Necrosis Factor-alpha; C086539:BQ 788; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D005978:Glutathione; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester