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

Abstract

We tested the hypothesis that superoxide anion (O(2)(-).) generated in the kidney by prolonged angiotensin II (ANG II) reduces renal cortical Po(2) and the use of O(2) for tubular sodium transport (T(Na):Q(O(2))). 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 Po(2) 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.ml(-1).min(-1).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 Po(2) in the proximal tubule (39 +/- 1 vs. 34 +/- 2 mmHg; P < 0.05) and throughout the cortex and reduced the T(Na):Q(O(2)) (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 p22(phox), and reduced expression of EC-SOD can be ascribed to O(2)(-). generation because they are prevented by an SOD mimetic.

Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis

“…Of note, oxidative stress per se aggravates hypoxia in the kidney. Oxidative stress reduces the efficiency of oxygen use by disturbing mitochondrial respiration, thereby contributing to the resulting hypoxia in the kidney (30,49). The consumption of vasodilatory nitric oxide by oxidative stress can also result in a decrease in kidney blood flow, further aggravating renal hypoxia.…”

Activation of the Renin-Angiotensin System and Chronic Hypoxia of the Kidney

“…Specifically, angiotensin II reduced the efficiency of renal oxygen usage in tubular sodium transport, resulting in a decrease in oxygen tension throughout the cortex. Tempol blunted all these effects of angiotensin II (55). Further, Adler and Huang showed that NO bioavailability in SHR is impaired due to an angiotensin II-mediated increase in superoxide production in association with enhanced expression of NADPH oxidase components (56).…”

Chronic Hypoxia and Tubulointerstitial Injury

“…Kidneys of the spontaneously hypertensive rat (SHR), which characteristically undergo oxidative stress, revealed enhanced oxygen usage relative to tubular sodium transport and lower intrarenal pO 2 (45). Amelioration of oxidative stress improved renal oxygenation in a model of diabetic nephropathy (46) and in the angiotensin II continuous infusion model (47). The same oxidative stress-related mechanism may cause tubulointerstitial hypoxia in the aging kidney (48).…”