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Effects of angiotensin II receptor blockade on proximal fluid uptake in the rat kidney
Author(s) -
Smart M L,
Hiranyachattada S,
Harris P J
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702366
Subject(s) - losartan , candesartan , angiotensin ii , chemistry , endocrinology , medicine , tubular fluid , kidney , endogeny , renin–angiotensin system , receptor , proximal tubule , blood pressure
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 AT 1 antagonists (losartan, EXP3174, candesartan). Addition of losartan at 10 −8 M decreased fluid uptake rate (Jv a ) 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.British Journal of Pharmacology (1999) 126 , 697–700; doi: 10.1038/sj.bjp.0702366