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

摘要

class="enumerated" style="list-style-type:decimal">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.