Effects of angiotensin II receptor blockade on proximal fluid uptake in the rat kidney

Abstract

Angiotensin II has a well described dose-dependent biphasic action on proximal tubule fluid uptake, although the concentration and effect of endogenous luminal angiotensin II remain controversial. Shrinking split-droplet micropuncture was used to examine the fluid uptake in response to the luminal application of three AT1 antagonists (losartan, EXP3174, candesartan). Addition of losartan at 10(-8) M decreased fluid uptake rate (Jva) by 17.5+/-2.2% (P<0.05). Luminal addition of EXP3174 at concentrations between 10(-9)-10(-5) M caused a dose-dependent decrease in fluid uptake, with a maximum decrease of 41.0+/-9.5% (P<0.01) at 10(-6) M. Candesartan also decreased fluid uptake, by 21.9+/-4.9% (P<0.05) at 10(-8) M and 23.6+/-5.5% (P<0.05) at 10(-5) M. All three antagonists at a low concentration (10(-8) M) decreased fluid uptake. EXP3174 and candesartan at a higher concentration (10(-5) M) also decreased fluid uptake in contrast to the previously reported effect of losartan. We conclude that the endogenous concentration of antiotensin II in the proximal luminal fluid is low and exerts a stimulatory effect on fluid absorption. Losartan at concentrations greater than 10(-6) M may have a non-selective action on fluid uptake.

Figure 1

The effect of intratubular AT₁ antagonists on proximal tubular fluid absorption. Data are shown as means±s.e.mean and presented as percentage changes in fluid absorption compared with control. Figures in parentheses indicate numbers of animals. ^*P<0.05, ^**P<0.01 (paired t-test).