Vasopressin stimulates the production of extracellular matrix by cultured rat mesangial cells

1. Mesangial expansion, an indicator of chronic glomerular diseases, occurs as a result of the excessive accumulation of extracellular matrix (ECM) proteins, such as type IV collagen. In order to investigate the ability of vasopressin (AVP), which causes mesangial cell proliferation and hypertrophy, to induce ECM production, an enzyme-linked immunosorbent assay was used to measure type I and IV collagen and fibronectin produced from cultured rat mesangial cells. 2. Addition of AVP (0.01-1000 nmol/L) caused a significant and concentration-dependent production of secreted and cell-associated ECM, type I collagen, type IV collagen and fibronectin by cultured rat mesangial cells. The AVP V(1A) receptor-selective antagonist YM218 (0.01-1000 nmol/L) potently and concentration-dependently inhibited the induced increase in ECM production caused by AVP, but the V(2) receptor-selective antagonist SR 121463A (0.1-1000 nmol/L) did not potently inhibit. 3. Vasopressin inhibited the synthesis of matrix metalloproteinase (MMP)-2, which degrades matrix proteins, including type IV collagen, and stimulated endothelin (ET)-1 secretion from mesangial cells. These effects were potently inhibited by YM218, but not by SR 121463A. 4. In addition, 10 nmol/L ET-1 inhibited the synthesis of MMP-2 and stimulated ECM production in mesangial cells. These effects were completely abolished by the ET(A) receptor-selective antagonist YM598 (1 micromol/L); however, the ET(B) receptor-selective antagonist BQ-788 (1 micromol/L) and the AVP receptor antagonists YM218 and SR 121463A did not inhibit ET-1-induced inhibition of MMP-2 synthesis and ECM production. In addition, AVP-induced inhibition of MMP-2 synthesis and ECM production were partly inhibited by YM598. 5. These findings indicate that AVP may modulate ECM production not only via a direct action on V(1A) receptors, but also through stimulation of ET-1 secretion. Vasopressin may contribute to the glomerular remodelling and ECM accumulation observed in glomerular diseases.