Effects of chronic administration of somatostatin analogue SMS 201-995 on the progression of chronic renal failure in subtotal nephrectomized rats.

The recent study has demonstrated the presence of somatostatin (SRIF) secretory cells in the rat glomerulus. Because of the polyvalent actions of this peptide, SRIF may play some roles in the evolution of chronic renal failure. The present study evaluated the effects of a long acting SRIF analogue, SMS 201-995 on the progression of renal failure in 3/4 nephrectomized (NPX) rats. Animals were divided into four groups; (1) normal control (C) (n = 9), (2) NPX-C (n = 10), (3) NPX treated with SMS 201-995 (0.5 micrograms/day) (NPX-0.5) (n = 9) and (4) NPX with SMS 201-995 (5.0 micrograms/day) (NPX-5.0) (n = 9). This drug was subcutaneously given daily for 6 weeks. Periodic observations were done at 0, 3 and 6 weeks. Both hematocrit and systolic blood pressure showed significant fall and rise, respectively, in NPX rats compared with C at 3 and 6 weeks. Also both serum creatinine and blood urea nitrogen in these groups elevated significantly at 3 and 6 weeks compared with C. Not significant changes were observed in the 24-h urine volume among the NPX rats. At 6 weeks, the urinary protein excretion in NPX-5.0 was significantly less than those in NPX-C and NPX-0.5 rats. Urinary sodium excretion in NPX-5.0 was significantly lower than that in NPX-C. Histologic examination of the kidney showed less proliferation of mesangial cells in NPX-5.0 than NPX-C. These results suggest that SMS 201-995 may limit the rate of progression of chronic renal failure in this experimental model.