Angiotensin II Reduces Transport-Dependent Oxygen Consumption but Increases Transport-Independent Oxygen Consumption in Immortalized Mouse Proximal Tubular Cells
2014 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, Vol. 812, 157-163 p.Article in journal (Refereed) Published
Oxidative stress is closely associated with renal dysfunction following diabetes and hypertension. Angiotensin II (Ang II) can activate the NADPH-oxidase, increasing oxidative stress that is thought to blunt proximal tubular electrolyte transport and thereby oxygen consumption (QO(2)). We investigated the effect of Ang II on QO(2) in immortalized mouse proximal tubular cells over-expressing the NADPH oxidase subunit p22(phox); a model of increased oxidative stress. Cultured cells were exposed to either Ang II or H2O2 for 48 h. QO(2) was determined during baseline (113 mmol/l NaCl; transport-dependent QO(2)) and during sodium-free conditions (transport-independent QO(2)). Ang II reduced transport-dependent QO(2) in wild-types, but not in p22(phox) which also displayed increased QO(2) at baseline. Transport-independent QO(2) was increased in p22(phox) and Ang II had no additional effect, whereas it increased QO(2) in wild-type. Addition of H2O2 reduced transport-dependent QO(2) in wild-types, but not in p22(phox). Transport-independent QO(2) was unaffected by H2O2. The similar effects of Ang II and H2O2 to reduce transport-dependent QO(2) suggest a direct regulatory role of oxidative stress. In accordance, the transport-dependent QO(2) was reduced in p22(phox) already during baseline. The effects of Ang II on transport-independent QO(2) was not replicated by H2O2, indicating direct regulation via Ang II-receptors independently of oxidative stress. However, the Ang II effect was absent in p22(phox), suggesting that oxidative stress also modulates normal Ang II signaling. In conclusion, Ang II affects both transport-dependent and transport-independent QO(2) in proximal tubular cells and may be an important pathway modulating renal QO(2).
Place, publisher, year, edition, pages
Kluwer Academic Publishers , 2014. Vol. 812, 157-163 p.
Proximal tubule cell; Oxidative stress; Angiotensin-II; Oxygen consumption; Electrolyte transport
IdentifiersURN: urn:nbn:se:liu:diva-113037DOI: 10.1007/978-1-4939-0620-8_21ISI: 000345121200022PubMedID: 24729228ISBN: 978-1-4939-0620-8; 978-1-4939-0583-6OAI: oai:DiVA.org:liu-113037DiVA: diva2:778372
41st Annual Meeting of the International-Society-on-Oxygen-Transport-to-Tissue (ISOTT)