Roles of Oxidative Stress and AT 1 Receptors in Renal Hemodynamics and Oxygenation in the Postclipped 2K,1C Kidney

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Abstract
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 2α (PGF 2α ) 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 2α 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.