Mesangial expansion is one of the histological abnormalities observed among the various glomerular diseases. It is due largely to the accumulation of extracellular matrix (ECM) proteins, such as type IV collagen, laminin and fibronectin. In order to examine the abilities of mesangial cells to produce type IV collagen, we used enzyme-linked immunosorbent assay to measure type IV collagen secreted from cultured rat mesangial cells. After exposing confluent cells to endothelin-1 (ET-1, 0.01 microM), insulin-like growth factor-1 (100 ng/ml) angiotensin-II (1 microM) and transforming growth factor-beta (1 ng/ml) for 24 hours, type IV collagen production increased 1.5 approximately 2.5 times. ET-1 stimulated type IV collagen production in a dose-dependent fashion, and this effect was blocked by the protein kinase C inhibitor, staurosporine. Atrial natriuretic peptide (ANP) inhibited the increase in type IV collagen production caused by ET-1 in a dose-dependent fashion. Addition of 8-bromo-cGMP similarly suppressed the stimulation of type IV collagen production caused by ET-1. These findings indicate that ET-1 stimulates type IV collagen synthesis in cultured rat mesangial cells by a mechanism probably involving activation of PKC, and that ANP inhibits ET-1-induced production of type IV collagen through a cGMP-dependent process.