Losartan antagonism of angiotensin-II-induced potassium secretion across rat colon

 The effect of angiotensin II (ANG II) on potassium transport across the short-circuited rat distal colon was investigated using ⁸⁶Rb⁺ as a tracer for unidirectional K⁺ fluxes. The addition of high concentrations of ANG II (≥10^–6 M) to the serosal bathing solution had no effect on the mucosal to serosal flux of Rb⁺, but significantly increased the serosal to mucosal flux and abolished the basal net absorptive Rb⁺ flux. These ANG-II-induced alterations in Rb⁺ transport were blocked by the AT₁ receptor antagonist losartan and its metabolite EXP3174, which is also known to have AT₁ receptor antagonistic activity. In contrast, an AT₂ receptor antagonist, PD123319, did not prevent the alterations in colonic Rb⁺ transport induced by ANG II in vitro. At lower bath concentrations (10^–7 M to 10^–10 M ), ANG II had no measurable effects on Rb⁺ transport across this tissue but ANG II did have a bimodal effect on short-circuit current (I _sc), indicating additional effects on the electrogenic transport of other ions. Dose-dependent reductions in I _sc were observed between 10^–7 M (↓ΔI _sc=1.96±0.49 μEq·cm^–2·h^–1, n=6) and 10^–10 M (↓ΔI _sc=0.16±0.19 μEq·cm^–2·h^–1, n=7) ANG II, whereas I _sc was increased at the higher concentrations (↑ΔI _sc= 3.36±0.52 μEq·cm^–2·h^–1, n=7, at 10^–4 M). The ANG-II-induced increases and decreases in I _sc were both blocked by losartan but not by PD123319. These studies are the first to demonstrate an effect of ANG II on K⁺ transport across rat colon that is independent of aldosterone and mediated by AT₁ receptors. Received: 13 March 1998 Received after revision and accepted: 26 May 1998