Roles of Oxidative Stress and AT1 Receptors in Renal Hemodynamics and Oxygenation in the Postclipped 2K,1C Kidney

WJ Welch, M Mendonca, S Aslam, CS Wilcox - Hypertension, 2003 - Am Heart Assoc
WJ Welch, M Mendonca, S Aslam, CS Wilcox
Hypertension, 2003Am Heart Assoc
The spontaneously hypertensive rat (SHR) exhibits angiotensin II (Ang II)–dependent
oxidative stress and reduced efficiency of renal oxygen usage (QO2) for tubular sodium
transport (TNa). We tested the hypothesis that oxidative stress determines the reduced TNa:
QO2 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 …
The spontaneously hypertensive rat (SHR) exhibits angiotensin II (Ang II)–dependent oxidative stress and reduced efficiency of renal oxygen usage (QO2) for tubular sodium transport (TNa). We tested the hypothesis that oxidative stress determines the reduced TNa:QO2 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 (PGF) and malondialdehyde (MDA) and renal oxygenation from pO2 in the renal cortex and from the ratio of calculated TNa and QO2 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 and MDA were higher in 2K,1C vehicle-treated rats compared with Sham and were normalized by Temp. The pO2 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 TNa:QO2 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 O2 for Na+ transport, independent of the fall in blood pressure.
Am Heart Assoc