Effect of a nonpeptide vasopressin V1 antagonist (OPC-21268) on experimental accelerated focal glomerulosclerosis
Related Experiment Videos
1Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
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.
Insights
A vasopressin V1 receptor antagonist, OPC-21268, reduced kidney damage in rats with progressive focal glomerulosclerosis. This suggests vasopressin V1 receptors are key in glomerulosclerosis development and progression.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Physiology
Background:
- Spontaneously hypercholesterolemic (SHC) rats develop progressive focal glomerulosclerosis (FGS) with hypercholesterolemia and proteinuria.
- Unilateral nephrectomy accelerates FGS development in SHC rats.
Purpose of the Study:
- To investigate the therapeutic potential of the nonpeptide orally effective vasopressin V1 receptor antagonist OPC-21268 in a rat model of progressive FGS.
Main Methods:
- SHC rats underwent unilateral nephrectomy to induce FGS.
- Rats were treated with OPC-21268 (1% in chow) for 9 weeks post-nephrectomy.
- Biochemical markers (triglyceride, creatinine, BUN, creatinine clearance) and histological parameters (glomerular sclerosis index) were assessed.
Main Results:
- OPC-21268 treatment significantly reduced increases in triglyceride, systolic blood pressure, serum creatinine, and BUN.
- Creatinine clearance deterioration was prevented in the OPC-21268 group.
- Histological analysis revealed a significant decrease in the glomerular sclerosis index in OPC-21268 treated rats.
Conclusions:
- Vasopressin, acting through V1 receptors, plays a significant role in the pathogenesis of glomerulosclerosis.
- Vasopressin V1 receptor antagonism with OPC-21268 demonstrates potential in preventing renal injury progression in FGS.