Cardiorenal protection in experimental hypertension with renal failure: comparison between vasopeptidase inhibition and angiotensin receptor blockade

Objective: The aim of the present study was to compare the preventive impact of treatment with a vasopeptidase inhibitor (VPI) with an angiotensin-receptor blocker (ARB) on left ventricular (LV) function and renal damage in rats with renal failure after 5/6 renal ablation (Nx). Methods: Rats (n = 15-20, each group) underwent either sham-operation (Sham) or 5/6 renal ablation (Nx). Two additional groups of Nx-animals (groups Nx-VPI and Nx-ARB) were treated with the VPI ilepatril (AVE7688, 30mgkg(-1) d(-1)) or with the ARB olmesartan (10 mg kg(-1) d(-1)). Animals were followed for 4 weeks. Results: Systolic blood pressure (SBP), LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) were increased 4 weeks after Nx (p<0.05). LV pressure rise (+dP/dt/LVPmax), LV pressure fall (-dP/dt/LVPmax), and creatinine clearance decreased, while albuminuria and renal glomerulosclerosis index (GSI) increased with Nx (p<0.05, respectively). In comparison to Nx, treatment with both VPI and ARB normalized SBP, LVH, LVEDP, +dP/dt/LVPmax, and -dP/dt/LVPmax to Sham control levels. GSI, but not creatinine clearance, was also normalized in response to both treatments. The significant increase in albuminuria observed in Nx (+230-fold versus Sham, p<0.0001) was partially reduced in Nx-VPI (+47-fold versus Sham, p<0.0001) and fully abolished in Nx-ARB. Conclusions: Both ilepatril and olmesartan conferred strong cardiorenal protective effects in rats with renal failure. While cardioprotection was clearly comparable with both treatment regimens, the ARB provided a better protection against the increase in albuminuria, although renal function and structural kidney changes were similarly affected by the VIP and ARB.