Effects of angiotensin inhibitors on renal injury and angiotensin receptor expression in early hypertensive nephrosclerosis

Angiotensin converting enzyme inhibitors (ACEI) are known to inhibit the progression of established renal failure. The aim of this study was to compare the efficacy of an ACEI and an AT1 receptor antagonist (AT1R-Ant) in preventing the development of renal disease, at an early stage of hypertensive nephrosclerosis. SHRSP/Izm rats (n = 61) were treated from 10 wk until 22 wk with the ACEI delapril (40 mg/kg/d) or the AT1R-Ant candesartan cilexetil (1 mg/kg/d). Proteinuria, and structural/ultrastructural changes were assessed at 14 and 22 wk. Treatment with either agent resulted in reductions in blood pressure and cardiovascular hypertrophy. Neither proteinuria nor major renal histological changes were evident at 14 wk. At 22 wk, however, proteinuria accompanied by nephrosclerotic changes was seen in the untreated SHRSP/Izm. Treatment with either ACEI or AT1R-Ant resulted in similar reductions in proteinuria (untreated, 32.2 +/- 7.4; delapril-treated, 5.5 +/- 1.2; candesartan-treated, 3.9 +/- 0.3 mg/100 g/d). Prominent sclerosis of small-to-medium sized renal arteries was seen in the untreated SHRSP/Izm at 22 wk, but was similarly attenuated by the ACEI and AT1R-Ant. The glomerular ultrastructure was comparable between the two groups. No significant changes in renal AT1a or AT1b receptor subtype mRNA expression were seen throughout the course of the study. In contrast, a decrease in AT2 receptor mRNA was seen in the drug-treated groups at 14 wk but not at 22 wk. These results suggest that both ACEI and AT1R-Ant have similar efficacy in attenuating the onset of renal injury in early hypertensive nephrosclerosis, and that treatment with either agent is associated with a transient decrease in AT2 receptor mRNA expression.