Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow

Tonja Emans, Ben Janssen, Maximillian Pinkham, Connie P C Ow, Roger Evans, Jaap Joles, Simon Malpas, C T Paul Krediet, Maarten Koeners

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)
243 Downloads (Pure)

Abstract

We 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 pO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical pO2 was dose-dependently reduced by intravenous AngII. Reductions in pO2 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 pO2. This could be reversed within minutes by pharmacological AT1 receptor 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.
Original languageEnglish
Pages (from-to)6287–6300
Number of pages14
JournalJournal of Physiology
Volume594
Issue number21
Early online date18 Aug 2016
DOIs
Publication statusPublished - 1 Nov 2016

Keywords

  • kidney
  • oxygenation
  • hypoxia
  • cortex
  • telemetry
  • angiotensin-II
  • phenylephrine
  • Cyp1a1Ren2 transgenic rat

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