Angiotensin receptor blockade has protective effects on the post-stenotic porcine kidney

Angiotensin converting enzyme inhibitors (ACEI)/ angiotensin-II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that ACEI/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with valsartan, or triple therapy (7 pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood-oxygen-level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly, however, valsartan did not change the GFR of the stenotic kidney compared to renal artery stenosis and was similar to triple therapy. Both valsartan and triple therapy stimulated microvascular density, and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function.