HEPARIN INHIBITS INDUCTION OF NITRIC-OXIDE SYNTHASE BY CYTOKINES IN RAT-BRAIN MICROVASCULAR ENDOTHELIAL-CELLS

The inflammatory reaction following ischemic brain injury involves bio active mediators released mainly from leukocytes. The aim of this in v itro-study was to evaluate possible modulatory actions of heparin on n itric oxide synthesis induced by proinflammatory cytokines. Rat microv ascular brain endothelial cells were isolated from adult rat brains an d treated with interferon-gamma (IFN-gamma) and interleukin-1 beta (IL -1 beta) with or without heparin. The expression of inducible nitric o xide synthase (iNOS) mRNA and the iNOS protein activity was analyzed b y reverse transcription polymerase chain reaction (RT-PCR) and Griess reagent, respectively. Heparin in a dose-dependent manner attenuated t he increase in iNOS expression and NO release after cytokine activatio n, Thus, in addition to its anticoagulatory effect, heparin may also b e effective in the prevention of inflammatory reaction after cerebral ischemia. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.