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Background/Aims: We have reported that the long-term administration of angiotensin II receptor blockers (ARBs) induced unusual proliferative changes of renal afferent arteriolar smooth muscle cells (SMCs) in rats, associated with the overproduction of renin. In this study, we examined that a direct renin inhibitor (DRI: Aliskilen; Novartis Pharma Co, USA) might induce different changes on afferent arteriolar walls compared to ARBs. Method: Twenty one 6-weeks-old male spontaneous hypertensive rats (SHRs) were divided into the following three groups: high-dose DRI group (n=7), low-dose DRI group (n=5) and control group (n=9). The rats were fed a standard diet (0.4%NaCl) containing high-dose (150mg/kg/day), low-dose (30mg/kg/day) DRI and without DRI for 12 weeks. The kidneys were examined by histological and immunohistochemical studies. Systolic blood pressure, 24-h urine samples and blood samples were also examined. Results: The afferent arteriolar SMC walls in the two DRI groups showed no proliferative changes. The positive renin expression area was the largest in the high-dose DRI group among the three groups (14.3±4.0µm2, 6.7±2.0µm2, 2.6±0.9µm2/glomerlus, p=0.020, p=0.008, p=0.017, respectively). Conclusion: The long-term DRI administration increases tissue and circulatory renin; however, afferent arteriolar proliferative changes as shown in ARBs were not induced.

Direct Renin Inhibitor is Better than Angiotensin II Receptor Blocker for Intrarenal Arterioles