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 Rb-86(+) as a tracer for unidirectional K+ fluxes. The addition of high concentrations of ANG II (greater than or equal to 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 AT(1) receptor antagonist losartan and its metabolite EXP3174, which is also known to have AT(1) receptor antagonistic activity. In contrast, an AT(2) 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,, were observed between 10(-7) M (down arrow Delta Isc = 1.96 +/- 0.49 mu Eq.cm(-2).h(-1), n = 6) and 10(-10) M (down arrow Delta I-sc = 0.16 +/- 0.19 mu Eq.cm(-2)h(-1), n=7) ANG II, whereas I-sc was increased at the higher concentrations (up arrow Delta I-sc = 3.36 +/- 0.52 mu Eq.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 AT(1) receptors.