Angiotensin II (Ang II) selectively regulates paracellular ionic and fluid permeability in proximal tubule (PT) cells

Abstract

Oxidative stress induced by Ang II or by inhibition of nitric oxide reduces renal efficiency of O2 usage to transported Na+. Furthermore, high Ang II reduced net Na+ uptake in PT cells. We tested the hypothesis that Ang II-induced oxidative stress increases paracellular permeability in PT cells. We measured transepithelial resistance (TER); an index of paracellular Na+ permeability and mannitol permeability; an index of paracellular fluid permeability. Immortalized mouse PT cells and in MDCK-I, a model of distal tubule (DT) cells, in monolayers grown on special plates, were treated with vehicle or Ang II (10 −8 to 10 −10 M). Ang II increased TER in MDCK (35–49 ohm) at all doses but decreased (15–22 ohm) TER in PT cells. Basal mannitol permeability was higher in PT cells compared to MDCK cells (PT: 7.89±0.6 vs. MDCK: 2.68±0.2 %/h, n=22–24, P<0.0001), but was reduced dose-dependently by Ang II in both PT and MDCK cells. In summary, physiological doses of Ang II increase paracellular Na+, but not fluid permeability selectively in the PT. An increase in Na+ backflux into the PT lumen may underlie both the reduced net Na+ reabsorption from the PT and the reduced efficiency of O2 use for net Na+ transport caused by Ang II.