Kurihara I, Saito T, Obara K, Shoji Y, Hirai M, Soma J, Sato H, Imai Y, Abe K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Nephron. 1996;73(4):629-36. doi: 10.1159/000189151.
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.
在患有高胆固醇血症和蛋白尿的自发性高胆固醇血症（SHC）大鼠中发生的进行性局灶性肾小球硬化（FGS）模型上，研究了非肽类口服有效的血管加压素V1受体拮抗剂OPC-21268的作用。7周龄时进行单侧肾切除术以加速自发性FGS的发展。肾切除术后，给服用OPC的大鼠喂食含1%OPC-21268的食物，持续9周。血管加压素V1拮抗剂治疗显著降低了甘油三酯水平、收缩压、血清肌酐和血尿素氮的升高速率，并防止了肌酐清除率的显著恶化。大鼠在16周龄时处死。组织学检查显示，OPC组的肾小球硬化指数与对照组相比显著降低（2.2±0.1对2.6±0.1，p<0.01）。与对照组相比，OPC组的相对间质体积和肾小球体积有减小的趋势。这些结果表明，血管加压素通过V1受体在肾小球硬化的发展中起重要作用，血管加压素V1拮抗剂可能预防肾小球硬化中肾损伤的进展。
