Key points Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary.We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats.This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.Exogenous angiotensin‐II reduced renal cortical tissue PnormalO2 more than equi‐pressor doses of phenylephrine, probably because it reduced renal oxygen delivery more than did phenylephrine.Activation of the endogenous renin–angiotensin system in transgenic Cyp1a1Ren2 rats reduced cortical tissue PnormalO2; in this model renal hypoxia precedes the development of structural pathology and can be reversed acutely by an angiotensin‐II receptor type 1 antagonist.Angiotensin‐II promotes renal hypoxia, which may in turn contribute to its pathological effects during development of chronic kidney disease. AbstractWe hypothesised that both exogenous and endogenous angiotensin‐II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PnormalO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PnormalO2 was dose‐dependently reduced by intravenous AngII. Reductions in PnormalO2 were significantly greater than those induced by equi‐pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3 ml min−1. Equi‐pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin–angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PnormalO2. This could be reversed within minutes by pharmacological angiotensin‐II receptor type 1 (AT1R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT1 receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease.
Blood pressure, renal hemodynamics, electrolyte, and water excretion all display diurnal oscillation. Disturbance of these patterns is associated with hypertension and chronic kidney disease. Kidney oxygenation is dependent on oxygen delivery and consumption that in turn are determined by renal hemodynamics and metabolism. We hypothesized that kidney oxygenation also demonstrates 24-h periodicity. Telemetric oxygen-sensitive carbon paste electrodes were implanted in Sprague-Dawley rats (250–300 g), either in renal medulla (n = 9) or cortex (n = 7). Arterial pressure (MAP) and heart rate (HR) were monitored by telemetry in a separate group (n = 8). Data from 5 consecutive days were analyzed for rhythmicity by cosinor analysis. Diurnal electrolyte excretion was assessed by metabolic cages. During lights-off, oxygen levels increased to 105.3 ± 2.1% in cortex and 105.2 ± 3.8% in medulla. MAP was 97.3 ± 1.5 mmHg and HR was 394.0 ± 7.9 bpm during lights-off phase and 93.5 ± 1.3 mmHg and 327.8 ± 8.9 bpm during lights-on. During lights-on, oxygen levels decreased to 94.6 ± 1.4% in cortex and 94.2 ± 8.5% in medulla. There was significant 24-h periodicity in cortex and medulla oxygenation. Potassium excretion (1,737 ± 779 vs. 895 ± 132 μmol/12 h, P = 0.005) and the distal Na+/K+ exchange (0.72 ± 0.02 vs. 0.59 ± 0.02 P < 0.001) were highest in the lights-off phase, this phase difference was not found for sodium excretion (P = 0.4). It seems that oxygen levels in the kidneys follow the pattern of oxygen delivery, which is known to be determined by renal blood flow and peaks in the active phase (lights-off).
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