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(Hypertension. 2003;41:692.)
© 2003 American Heart Association, Inc.

Scientific Contributions

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

From the Division of Nephrology and Hypertension and Center for Hypertension and Renal Disease Research, Georgetown University Medical Center, Washington, DC.

Correspondence to William J. Welch, PhD, Georgetown University Medical Center, 4000 Reservoir Rd NW, Building D, Room 395, Washington, DC 20007. E-mail welchw{at}georgetown.edu

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 F₂ (PGF₂) and malondialdehyde (MDA) and renal oxygenation from pO₂ 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-PGF₂ 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 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 O₂ for Na⁺ transport, independent of the fall in blood pressure.

Key Words: hypertension, renovascular • Goldblatt hypertension • renal artery • nitric oxide

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