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The inhibition of the angiotensin-converting enzyme arrests the retention of Na and water and elevation of mean arterial blood pressure during the lowering of the renal perfusion pressure. This prevention is possible because of the captopril-induced decrease in angiotensin II and plasma aldosterone contents.

The resetting of input-output balances during reduction of renal perfusion pressure (rRPP) may result from factors such as a decline in plasma aldosterone concentration, shifts in intrarenal hemodynamics, an enhancement in atrial natriuretic factor and physical factors. This is evident because servo control of rRPP ensures that enhanced system mean systemic blood pressure does not exercise direct pressure effects on the kidneys.

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, 30 mg kg−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 (+d P/d t/LVPmax), LV pressure fall (−d P/d t/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, +d P/d t/LVPmax, and −d P/d t/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. [ABSTRACT FROM AUTHOR]

BackgroundLow nephron number is a recently identified cause of arterial hypertension. We set out to test the effect of nephron number dosing on blood pressure and cardiorenal damage including left ventricular (LV) remodeling and function. Because exact determination of nephron number in vivo is currently not possible, we combined the Munich Wistar Frömter (MWF) genetic rat model of inborn nephron deficit with the 5/6 renal ablation model (Nx).MethodsTo obtain distinct levels of nephron number dose (NND), rats underwent either sham-operation (Wistar-Sham NND 1.0, and MWF-Sham NND 0.6, n = 15, respectively) or 5/6 renal ablation (Nx, Wistar-Nx NND 0.17, and MWF-Nx NND 0.1, n = 20, respectively). Two additional groups were treated orally for 4 weeks with 1 mg/kg/day ramipril (Wistar-Nx-ACEI and MWF-Nx-ACEI, n = 15, respectively).ResultsSystolic blood pressure (SBP), LV hypertrophy, mRNA expression of atrial natriuretic factor, LV contractility, and relaxation were exponentially correlated with NND (P < 0.0001, respectively). Creatinine clearance (ClCr) decreased, albuminuria, renal interstitial fibrosis, tubulointerstitial damage, and glomerulosclerosis index increased with lowering NND in both Wistar-Nx (NND 0.17) and MWF-Nx (NND 0.1) animals. LV perivascular and interstitial fibrosis and sarcoplasmic reticular (SR) Ca2+ cycling were not directly related to NND. Angiotensin-converting enzyme (ACE) inhibition with ramipril demonstrated strong cardio- and renoprotective effects even in the setting of very low NND of 0.1 in MWF-Nx animals.ConclusionsThese data demonstrate that reduced nephron number is a significant, independent determinant of blood pressure, cardiorenal damage, and LV dysfunction in a direct dose-dependent way.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.206 [ABSTRACT FROM AUTHOR]