Aldosterone blunts tubuloglomerular feedback by activating macula densa mineralocorticoid receptors.
Chronic aldosterone administration increases glomerular filtration rate, whereas inhibition of mineralocorticoid receptors (MRs) markedly attenuates glomerular hyperfiltration and hypertension associated with primary aldosteronism or obesity. However, the mechanisms by which aldosterone alters glomerular filtration rate regulation are poorly understood. In the present study, we hypothesized that aldosterone suppresses tubuloglomerular feedback (TGF) via activation of macula densa MR. First, we observed the expression of MR in macula densa cells isolated by laser capture microdissection and by immunofluorescence in rat kidneys. Second, to investigate the effects of aldosterone on TGF in vitro, we microdissected the juxtaglomerular apparatus from rabbit kidneys and perfused the afferent arteriole and distal tubule simultaneously. Under control conditions, TGF was 2.8±0.2 μm. In the presence of aldosterone (10(-8) mol/L), TGF was reduced by 50%. The effect of aldosterone to attenuate TGF was blocked by the MR antagonist eplerenone (10(-5) mol/L). Third, to investigate the effect of aldosterone on TGF in vivo, we performed micropuncture, and TGF was determined by maximal changes in stop-flow pressure P(sf) when tubular perfusion rate was increased from 0 to 40 nL/min. Aldosterone (10(-7) mol/L) decreased ΔP(sf) from 10.1±1.4 to 7.7±1.2 mm Hg. In the presence of l-NG-monomethyl arginine citrate (10(-3) mol/L), this effect was blocked. We conclude that MRs are expressed in macula densa cells and can be activated by aldosterone, which increases nitric oxide production in the macula densa and blunts the TGF response.
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216, USA.
Yiling
Y
Fu
John E
JE
Hall
Deyin
D
Lu
Lin
L
Lin
R Davis
RD
Manning
Liang
L
Cheng
Celso E
CE
Gomez-Sanchez
Luis A
LA
Juncos
Ruisheng
R
Liu
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D005246:Feedback / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D009569:Nitric Oxide; D000450:Aldosterone