Renoprotection by nitric oxide donor and lisinopril in the remnant kidney model

Previous studies showed a renoprotective effect of L-arginine in experiment al uremia. Whether this was caused by an increased nitric oxide (NO) releas e or depended on L-arginine per se is not clear. Here, we evaluated whether chronic administration of an NO donor, molsidomine, controlled systemic bl ood pressure and renal disease progression and prolonged survival In rats w ith renal mass reduction (RMR). Rats with RMR received the following daily in the drinking water: group 1 (n = 21), no specific therapy (vehicle); gro up 2 (n = 12), molsidomine, 120 mg/L; group 3 (n = 9), lisinopril, 25 mg/L; and group 4 (n = 12), reserpine, 5 mg/L, hydralazine, 80 mg/L, and hydroch lorothiazide, 25 mg/L, from day 21 after surgery, when rats had hypertensio n and proteinuria, until the death of the vehicle-treated rats. Molsidomine normalized systemic hypertension, only partially reduced proteinuria and s erum creatinine levels, but significantly prolonged animal survival, partic ularly in the early stage of the disease. Lisinopril at a similar systemic blood pressure was even better than molsidomine in limiting proteinuria, pr eserving renal function, and prolonging survival, but triple therapy, despi te being effective on blood pressure, offered no renoprotection or prolonge d survival. Endothelin-1 (ET-1) levels, formed in excessive amounts by the kidneys of these animals, were reduced by molsidomine and lisinopril, but n ot by triple therapy. The prolongation of survival by NO donor could be att ributed to its effect of reducing ET levels, which in turn may limit the sm ooth muscle cell proliferation and matrix accumulation responsible for orga n and, especially, myocardial fibrosis in uremia. (C) 1999 by the National Kidney Foundation, Inc.