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Cardiac fibroblasts (CFs) produce extracellular matrix proteins and participate in the remodeling of the heart. It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix turnover. In this study, we examined the production of BNP in adult canine CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs). BNP mRNA was detected in CFs, and a specific radioimmunoassay demonstrated that BNP_1-32 was secreted into the media at a rate of 11.2±1.0 pg/10⁵ cells per 48 hours (mean±SEM). The amount of BNP secretion was significantly (P<0.01) augmented by 10⁻⁷ mol/L tumor necrosis factor-α in a time-dependent manner. BNP significantly (P<0.01) inhibited de novo collagen synthesis as assessed by [³H]proline incorporation, whereas zymographic MMP-2 (gelatinase …