Role of Transforming Growth Factor-b1 in Cardiovascular Inflammatory Changes Induced by Chronic Inhibition of Nitric Oxide Synthesis

We previously reported that chronic inhibition of nitric oxide (NO) synthesis with N-nitro-L-arginine methyl ester (L-NAME) induces inflammatory changes (monocyte infiltration, myofibroblast formation, and monocyte chemoattractant protein-1 [MCP-1] and transforming growth factor-b1 [TGF-b1] expression) in the rat heart and vessel. There is debate regarding whether TGF-b1 exhibits proinflammatory or anti-inflammatory activities. We used the rat model to investigate the role of TGF-b in the pathogenesis of such inflammatory changes. We show here that infiltrating monocytes and myofibroblasts in the inflammatory lesions produced TGF-b1 on the third day of L-NAME administration. Cotreatment with a monoclonal antibody against TGF-b1, but not with control IgG, prevented the L-NAME–induced cardiac inflammation. The antibody also significantly inhibited the gene expression of MCP-1, P-selectin, and intercellular adhesion molecule-1. In summary, the antibody against TGF-b1 prevented inflammatory changes in rat heart and vessel induced by chronic inhibition of NO synthesis, suggesting that increased production of TGF-b1 is involved in the inflammatory changes in this model. (Hypertension. 2000;35:86-90.)