Role of transforming growth factor-beta 1 in cardiovascular inflammatory changes induced by chronic inhibition of nitric oxide synthesis

We previously reported that chronic inhibition of nitric oxide (NO) synthes is with N-omega-nitro-L-arginine methyl ester (L-NAME) induces inflammatory changes (monocyte infiltration, myofibroblast formation, and monocyte chem oattractant protein-1 [MCP-1] and transforming growth factor-beta 1 [TGF-be ta 1] expression) in the rat heart and vessel. There is debate regarding wh ether TGF-beta 1 exhibits proinflammatory or anti-inflammatory activities. We used the rat model to investigate the role of TGF-beta in the pathogenes is of such inflammatory changes. We show here that infiltrating monocytes a nd myofibroblasts in the inflammatory lesions produced TGF-beta 1 on the th ird day of L-NAME administration. Cotreatment with a monoclonal antibody ag ainst TGF-beta 1, but not with control IgG, prevented the L-NAME-induced ca rdiac inflammation. The antibody also significantly inhibited the gene expr ession of MCP-1, P-selectin, and intercellular adhesion molecule-1. In summ ary, the antibody against TGF-beta 1 prevented inflammatory changes in rat heart and vessel induced by chronic inhibition of NO synthesis, suggesting that increased production of TGF-beta 1 is involved in the: inflammatory ch anges in this model.