Early, but not late therapy with a vasopressin V-1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy

Introduction. Vasopressin, mainly through the VIA-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V-1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I). Materials and methods. After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V-1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-1, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7). Results. In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44 +/- 7% and 59 +/- 8% respectively). ACE-I significantly decreased proteinuria (67 +/- 7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30 +/- 18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21 +/- 20% and 0%, respectively), ACE-1 significantly lowered proteinuria (92 +/- 2%) and a focal glomerulosclerosis (69 +/- 1%) lowering trend was observed. Conclusion. These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage