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

We tested the hypothesis that superoxide anion (O-2(-.)) generated in the kidney by prolonged angiotensin II (ANG II) reduces renal cortical PO2 and the use of O-2 for tubular sodium transport (T-Na: Q(O2)). 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 +/- 4 vs. 146 +/- 6 mmHg; P < 0.001), renal vascular resistance (42 +/- 3 vs. 65 +/- 7 mmHg center dot ml(-1) center dot min(-1) center dot 100 g(-1); P < 0.001), renal cortical NADPH oxidase activity (2.3 +/- 0.2 vs. 3.6 +/- 0.4 nmol O-2(-) .. min(-1) . mg(-1) protein; P < 0.05), mRNA and protein expression for p22(phox) (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 +/- 1 vs. 34 +/- 2 mmHg; P < 0.05) and throughout the cortex and reduced the T-Na: Q(O2) ( 17 +/- 1 vs. 9 +/- 2 mumol/mumol; 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 O-2 usage for Na+ transport, activation of NADPH oxidase, increased expression of p22phox, and reduced expression of EC-SOD can be ascribed to O-2(-.) generation because they are prevented by an SOD mimetic.