Angiotensin-induced defects in renal oxygenation: Role of oxidative stress

We tested the hypothesis that superoxide anion (O2) generated in the kidney by prolonged angiotensin II (ANG II) reduces renal cortical PO2 and the use of O2 for tubular sodium transport (TNa:QO2). Groups (n = 8--11) of rats received angiotensin II (ANG II, 200 ng kg-1 min-1 sc) or vehicle for 2 wk with concurrent infusions of a permeant nitroxide SOD mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, 200 nmol kg-1 min-1) or vehicle. Rats were studied under anesthesia with measurements of renal oxygen usage and PO2 in the cortex and tubules with a glass electrode. Compared with vehicle, ANG II increased mean arterial pressure (107 plus or minus 4 vs. 146 plus or minus 6 mmHg; P < 0.001), renal vascular resistance (42 plus or minus 3 vs. 65 plus or minus 7 mmHg ml-1 min-1 100 g-1; P < 0.001), renal cortical NADPH oxidase activity (2.3 plus or minus 0.2 vs. 3.6 plus or minus 0.4 nmol O2- min-1 mg-1 protein; P < 0.05), mRNA and protein expression for p22phox (2.1- and 1.8-fold respectively; P < 0.05) and reduced the mRNA for extracellular (EC)-SOD (1.8 fold; P < 0.05). ANG II reduced the PO2 in the proximal tubule (39 plus or minus 1 vs. 34 plus or minus 2 mmHg; P < 0.05) and throughout the cortex and reduced the TNa QO2 (17 plus or minus 1 vs. 9 plus or minus 2 mol/ mol; P < 0.001). Tempol blunted or prevented all these effects of ANG II. The effects of prolonged ANG II to cause hypertension, renal vasoconstriction, renal cortical hypoxia, and reduced efficiency of O2 usage for Na+ transport, activation of NADPH oxidase, increased expression of p22phox, and reduced expression of EC-SOD can be ascribed to O2 generation because they are prevented by an SOD mimetic. [PUBLICATION ABSTRACT]