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ROLE OF ANGIOTENSIN II IN MODULATING FLOW‐DEPENDENT BICARBONATE TRANSPORT IN MOUSE PROXIMAL TUBULES
Author(s) -
Du Zhaopeng,
Yan Qingshang,
Duan Yi,
Weinbaum Sheldon,
Weinstein Alan M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a842-c
Subject(s) - losartan , angiotensin ii receptor type 1 , chemistry , angiotensin ii , endocrinology , medicine , bicarbonate , reabsorption , renin–angiotensin system , sodium–hydrogen antiporter , nitrendipine , receptor , kidney , biochemistry , biology , calcium , sodium , organic chemistry , blood pressure
We have previously demonstrated that mouse proximal tubules in vitro respond to changes in luminal flow with proportional changes in Na + and HCO 3 − absorption and that flow‐dependent modulation of proximal tubule bicarbonate reabsorption is due to changes in both NHE3 and H‐ATPase activity within the luminal cell membrane. Since Angiotension II is one of the important autocrine hormones that regulate Na + and HCO 3 − transport in the proximal tubule, we examined flow‐dependent transport in AT1 receptor knockout mice as well as the effect of blockers of AT1, NHE3 and H‐ATPase. Mouse proximal tubule S 2 segments were microperfused in vitro at flow rates of 5 and 20nl/min in the absence and presence of losartan, EIPA or bafilomycin in the lumen. HCO 3 − (J HCO3 ) absorption was significantly lower under both flow rates in AT1 knockout compared to the wild‐type mice (see table). 1 Flow‐dependent Bicarbonate AbsorptionThe fractional increases in J HCO3 in the AT1 KO, the losartan treated, and the wild type mice were 100%, 130% and 94%, the absolute changes were 42.74, 57.76 and 58.5pmole/min/mm and were all comparable. When the components of J HCO3 were assessed using inhibitors, it was found that the fractional increases in J HCO3 were reduced 49% by EIPA plus losartan or by bafilomycin plus losartan in the wild‐type mice. We conclude that angiotensin II is not critical to the signal cascade that mediates flow‐dependent proton secretion, and that flow impacts transport by both NHE3 and the H‐ATPase comparably.