Chronic Direct Renin Inhibition with Aliskiren Prevents the Development of Hypertension in Cyp1a1‐Ren2 Transgenic Rats with Inducible ANG II‐Dependent Hypertension

Abstract

The present study was performed to determine the effects of chronic direct renin inhibition on blood pressure and renal hemodynamics in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension. Male Cyp1a1-Ren2 rats (n=6) were fed a normal diet containing 0.15% indole-3-carbinol (I3C) for 16 days to induce slowly progressive ANG II-dependent hypertension. Conscious systolic blood pressure (SBP) was measured daily using tail-cuff plethysmography. The rats were then anesthetized with pentobarbital sodium and surgically prepared for the measurement of mean arterial pressure (MAP) and renal hemodynamic function. In rats induced with I3C, SBP increased from 130±7 to 191±6 mmHg (P<0.001) by day 16. In a separate group of rats (n=6), chronic administration of aliskiren (30 mg/kg/day, sc) prevented the development of hypertension (113±5 vs. 114±5 mmHg, NS). Rats treated with aliskiren exhibited lower MAP (138±4 vs. 201±6 mmHg, P<0.001) and RVR (23±4 vs. 38±3 mmHg/ml/min.g, P<0.01), and higher RPF (4.22±0.23 vs. 2.56±0.21 ml/min.g, P<0.01) and GFR (1.19±0.07 vs. 0.78±0.08 ml/min.g, P<0.01) compared with induced rats not treated chronically with aliskiren. The present findings demonstrate that chronic direct renin inhibition with aliskiren prevents the development of ANG II-dependent hypertension and the associated decrease in renal hemodynamic function in Cyp1a1-Ren2 transgenic rats.