INFLUENCE OF ANTIINFLAMMATORY AND ANTIOXIDANT AGENTS ON ENDOTHELIAL PERMEABILITY ALTERATIONS INDUCED BY BRADYKININ

Increased vascular permeability to plasma proteins and altered hemodyn amics 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 infla mmatory 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 (NAG, an o xygen free radical scavenger), and allopurinol (a xanthine oxidase inh ibitor) was determined. Endothelial permeability was evaluated by dete rmining tissue water content (TWC), I-125-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 co ntent (TBC), measured by Cr-51-labeled red blood cells. The results in dicate that albumin flux significantly increased in the peritoneum, pa ncreas, stomach, PSI, DSI, colon, kidneys, liver, lungs, and brain, TB C significantly increased in the kidneys, liver, lungs, and heart, as well as in the intestine, and an increased ALI, assaying endothelial p ermeability considering local hemodynamic alterations was noted in the pancreas, kidneys, liver, lungs, PSI, and DSI in the group with BK al one. These changes were to varying degrees reversed by pretreatment wi th indomethacin, ibuprofen, N-acetyl-L-cysteine, or allopurinol, where the protective effect tended to be organ-dependent.