Roles of oxidative stress and AT1 receptors in renal hemodynamics and oxygenation in the postclipped 2K,1C kidney

The spontaneously hypertensive rat (SHR) exhibits angiotensin II (Ang II)-dependent oxidative stress and reduced efficiency of renal oxygen usage (Q(O2)) for tubular sodium transport (T-Na). We tested the hypothesis that oxidative stress determines the reduced T-Na :Q(O2) ratio in the clipped kidney of the early 2-kidney, 1-clip (2K,1C) Ang II-dependent model. One week after sham operation (Sham) or clip placement, 2K,1C rats received for 2 weeks either a vehicle, the superoxide dismutase mimetic tempol (Temp), or candesartan (Cand). Oxidative stress was assessed from excretion of 8-isoprostaglandin F-2alpha (PGF(2alpha)) and malondialdehyde (MDA) and renal oxygenation from pO(2) in the renal cortex and from the ratio of calculated T-Na and Q(O2) values. The mean arterial pressure (MAP) of Sham (113+/-6 mm Hg) was increased in 2K,1C vehicle-treated rats (148+/-4 mm Hg), but both Temp and Cand restored MAP to Sham levels. The excretions of 8-iso-PGF(2alpha) and MDA were higher in 2K,1C vehicle-treated rats compared with Sham and were normalized by Temp. The pO(2) of Sham (42+/-2 mm Hg) was lower in 2K,1C vehicle-treated animals (28+/-2 mm Hg). This was restored to Sham values by Temp (36+/-3 mm Hg) but not by Cand (28+/-2 mm Hg). The T-Na :Q(O2) of Sham (12.9+/-1.6) was reduced in 2K,1C vehicle-treated rats (9.7+/-2.8) and was restored to Sham values by Temp (13.7+/-2.5) but not by Cand (7.5+/-1.6). We conclude that the correction of oxidative stress in the 2K,1C model partially corrects renal cortical hypoxia and inefficient utilization of O-2 for Na+ transport, independent of the fall in blood pressure.