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.

Nasal high flow (NHF) is an efficient oxygenation tool for the treatment of respiratory failure. The study investigated the effect of breathing pattern on positive airway pressure and dead-space clearance by NHF. The breathing cycle during NHF was characterized in 27 patients with acute respiratory failure (ARF), stable COPD and after mechanical ventilation (post-MV) via tracheostomy where also pressure was measured in the trachea. Dead-space clearance was measured in airway models during different breathing patterns. NHF reduced the respiratory rate (RR) and TI/TE through prolonging the TE; the TI/TE ranged between ≤0.5 observed in the COPD patients and ~1.0 in the ARF patients. NHF via standard medium-sized cannula generated a low-level expiratory pressure proportional to NHF rate and breathing flow; the median generated PEEP was only 1.71 cmH2O at NHF 45 L/min. The dilution and purging of expired gas from a nasal cavity model were observed to occur at the end of expiration as the expiratory flow slowed and the dynamic pressure decreased. The higher RR with shorter end-expiratory period resulted in reduced dead-space clearance by NHF; 20 L/min cleared 43±2 ml at RR 15 min-1 vs. 9±5 ml at RR 45 min-1, P<0.001, which was increased at higher NHF rate. At lower RR the clearance was similar across the range of NHF rates 20 - 60 L/min. Higher NHF elevates positive airway pressure and at the increased RR can improve the clearance. This may enhance gas exchange and lead to a reduction in the work of breathing.

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Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, < 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%, < 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart.

Nasal high flow (NHF) is an emerging therapy for respiratory support, but knowledge of the mechanisms and applications is limited. It was previously observed that NHF reduces the tidal volume but does not affect the respiratory rate during sleep. The authors hypothesized that the decrease in tidal volume during NHF is due to a reduction in carbon dioxide (CO2) rebreathing from dead space. In nine healthy males, ventilation was measured during sleep using calibrated respiratory inductance plethysmography (RIP). Carbogen gas mixture was entrained into 30 l/min of NHF to obtain three levels of inspired CO2: 0.04% (room air), 1%, and 3%. NHF with room air reduced tidal volume by 81 ml, SD 25 ( P < 0.0001) from a baseline of 415 ml, SD 114, but did not change respiratory rate; tissue CO2 and O2 remained stable, indicating that gas exchange had been maintained. CO2 entrainment increased tidal volume close to baseline with 1% CO2 and greater than baseline with 3% CO2 by 155 ml, SD 79 ( P = 0.0004), without affecting the respiratory rate. It was calculated that 30 l/min of NHF reduced the rebreathing of CO2 from anatomical dead space by 45%, which is equivalent to the 20% reduction in tidal volume that was observed. The study proves that the reduction in tidal volume in response to NHF during sleep is due to the reduced rebreathing of CO2. Entrainment of CO2 into the NHF can be used to control ventilation during sleep. NEW & NOTEWORTHY The findings in healthy volunteers during sleep show that nasal high flow (NHF) with a rate of 30 l/min reduces the rebreathing of CO2 from anatomical dead space by 45%, resulting in a reduced minute ventilation, while gas exchange is maintained. Entrainment of CO2 into the NHF can be used to control ventilation during sleep.