Spontaneous remission of diabetes arrests progression of nephropathy in streptozotocin-treated spontaneously hypertensive rats

Abstract

Although antihypertensive therapy retards the progression of diabetic nephropathy associated with hypertension, it is not known whether glycemic control reverses or arrests diabetic nephropathy under untreated hypertension. We previously reported that spontaneous remission of diabetes occurred in the neonatal streptozotocin (STZ) model of spontaneously hypertensive rats (SHR) after 28 weeks of age, whereas hypertension persisted. Thus, we studied diabetic nephropathy before and after the recovery from hyperglycemia in this model. Two-day-old male SHR were injected intraperitoneally with STZ or vehicle for control. Hypertension was developed and maintained in both STZ and control groups in a similar degree. Before the amelioration of hyperglycemia, urinary albumin excretion increased progressively in STZ-treated SHR as compared with control (24 weeks; 1.6 ± 0.5 mg/day, 17.5 ± 2.3 mg/day, P < 0.001), and renal and glomerular hypertrophies were seen with mesangial expansion in STZ-treated SHR. However, along the recovery from hyperglycemia, urinary albumin excretion did not increase in the STZ-treated group, while it consistently increased in the control group (52 weeks; 25.4 ± 10.0 mg/day, 29.7 ± 11.4 mg/day, not significant). Furthermore, there were no significant differences in renal weight, glomerular tuft area, and the incidence of glomerular sclerosis between the two groups at 52 weeks of age. This study suggests that glycemic control may be effective for diabetic nephropathy even in the coexistence of untreated hypertension.