Abstract
The effects of the nonpeptide orally effective vasopressin V1 receptor antagonist OPC-21268 were studied in progressive focal glomerulosclerosis (FGS) which developed in spontaneously hypercholesterolemic (SHC) rats with manifestations of hypercholesterolemia and proteinuria. Unilateral nephrectomy was performed at 7 weeks of age to accelerate spontaneous FGS. After nephrectomy, OPC-administered rats were fed chow containing 1% OPC-21268 for 9 weeks. Treatment with vasopressin V1 antagonist significantly reduced the rate of increase in the levels of triglyceride, systolic blood pressure, serum creatinine and BUN, and prevented a significant deterioration in creatinine clearance. Rats were sacrificed at 16 weeks of age. Histologically, the index of glomerular sclerosis in the OPC group showed a significant decrease compared to that in the control group (2.2 +/- 0.1 vs. 2.6 +/- 0.1, p < 0.01). Relative interstitial volume and glomerular volume in the OPC group showed a tendency to decrease compared to those in the control group. These results indicate that vasopressin plays an important role through V1 receptors in the development of glomerulosclerosis, and vasopressin V1 antagonist may prevent the progression of renal injury in glomerulosclerosis.
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