Spontaneously reduced blood pressure load in the rat streptozotocin-induced diabetes model: potential pathogenetic relevance

Abstract

The rat streptozotocin (STZ)-induced diabetes model is widely used to investigate the pathogenesis of diabetic nephropathy. However, overt nephropathy is inexplicably slow to develop in this model compared with renal mass reduction (RMR) models. To examine whether blood pressure (BP) differences correlated with the time course of glomerulosclerosis (GS), BP was measured continuously throughout the course by radiotelemetry in control ( n = 17), partially insulin-treated STZ-diabetes (average blood glucose 364 ± 15 mg/dl; n = 15), and two normotensive RMR models (systolic BP <140 mmHg)—uninephrectomy (UNX; n = 16) and 3/4 RMR by surgical excision [right nephrectomy + excision of both poles of left kidney (RK-NX); n = 12] in Sprague-Dawley rats. Proteinuria and GS were assessed at ∼16–20 wk (all groups) and at 36–40 wk (all groups except RK-NX). At 16 wk, significantly greater proteinuria and GS had developed in the RK-NX group compared with the other three groups (not different from each other). By 36–40 wk, substantial proteinuria and GS had also developed in the UNX group, but both the control and the STZ-diabetic rats exhibited comparable modest proteinuria and minimal GS. Systolic BP (mmHg) was significantly reduced in the STZ-diabetic rats (116 ± 1.1) compared with both control (124 ± 1.0) and RMR (128 ± 1.2 and 130 ± 3.0) groups ( P < 0.01). Similarly, “BP load” as estimated by BP power spectral analysis was also lower in the STZ-diabetic rats. Given the known protective effects of BP reductions on the progression of diabetic nephropathy, it is likely that this spontaneous reduction in ambient BP contributes to the slow development of GS in the STZ-diabetes model compared with the normotensive RMR models.