Influence of anti-inflammatory and antioxidant agents on endothelial permeability alterations induced by bradykinin.
Increased vascular permeability to plasma proteins and altered hemodynamics at the site of inflammation are characteristics of inflammation. In the present study, alterations in endothelial barrier permeability were evaluated in different organs/tissues 6 h after a systemic inflammatory response induced by intravenous injection of bradykinin (BK; 1.7 mg/kg). The effect of intravenous pretreatment with indomethacin or ibuprofen (cyclooxygenase inhibitors), N-acetyl-L-cysteine (NAC, an oxygen free radical scavenger), and allopurinol (a xanthine oxidase inhibitor) was determined. Endothelial permeability was evaluated by determining tissue water content (TWC), 125I-labeled human serum albumin (HSA) flux, and albumin leakage index (ALI) in various organs/tissues. The vasodilation in the local tissues was reflected by tissue blood content (TBC), measured by 51Cr-labeled red blood cells. The results indicate that albumin flux significantly increased in the peritoneum, pancreas, stomach, PSI, DSI, colon, kidneys, liver, lungs, and brain, TBC significantly increased in the kidneys, liver, lungs, and heart, as well as in the intestine, and an increased ALI, assaying endothelial permeability considering local hemodynamic alterations was noted in the pancreas, kidneys, liver, lungs, PSI, and DSI in the group with BK alone. These changes were to varying degrees reversed by pretreatment with indomethacin, ibuprofen, N-acetyl-L-cysteine, or allopurinol, where the protective effect tended to be organ-dependent.
Deng
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X
Department of Surgery, Lund University Hospital, Sweden.
Wang
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X
Andersson
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R
D000111:Acetylcysteine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001834:Body Water / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation; D007457:Iodine Radioisotopes; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014664:Vasodilation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016166:Free Radical Scavengers; D007457:Iodine Radioisotopes; D012709:Serum Albumin; D000493:Allopurinol; D001920:Bradykinin; D007052:Ibuprofen; D000111:Acetylcysteine; D007213:Indomethacin