PMID- 11880335
OWN - NLM
STAT- MEDLINE
DCOM- 20020419
LR  - 20171116
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 282
IP  - 4
DP  - 2002 Apr
TI  - Acute hypertension provokes internalization of proximal tubule NHE3 without 
      inhibition of transport activity.
PG  - F730-40
AB  - Acute hypertension rapidly decreases proximal tubule (PT) Na(+) reabsorption, 
      facilitated by a redistribution of PT Na(+)/H(+) exchangers (NHE3) out of the 
      apical brush border, increasing NaCl at the macula densa, the signal for 
      autoregulation of renal blood flow and GFR. This study aimed to determine whether 
      NHE3 activity per transporter decreases during acute hypertension and the time 
      dependence of the response. Blood pressure was elevated by 50-60 mmHg in male 
      Sprague-Dawley rats for 5 or 30 min by constricting arteries. Renal cortical 
      membranes were fractionated by density gradient centrifugation. NHE3 transport 
      activity was assayed as the rate of appearance of acridine orange (AO) from 
      AO-loaded vesicles in response to an inwardly directed Na(+) gradient. After 
      5-min hypertension, 20% of total NHE3 protein, assayed by immunoblot, 
      redistributed from low-density apical membranes to middensity membranes enriched 
      in intermicrovillar cleft markers; by 30 min, a similar percentage shifted to 
      heavier density membranes containing markers of endosomes. NHE3 activity shifted 
      to higher density membranes along with NHE3 protein, that is, no change in 
      activity/transporter during acute hypertension. Confocal analysis of NHE3 
      distribution also verified removal from apical microvilli and appearance in 
      subapical vesicles. We conclude that the decrease in renal PT Na(+) transport 
      during acute hypertension is mediated by removal of transport-competent NHE3 from 
      the apical brush border to subapical and internal reserves.
FAU - Yang, Li
AU  - Yang L
AD  - Department of Physiology and Biophysics, University of Southern California Keck 
      School of Medicine, Los Angeles, California 90089-9142, USA.
FAU - Leong, Patrick K K
AU  - Leong PK
FAU - Chen, Jennifer O
AU  - Chen JO
FAU - Patel, Nilem
AU  - Patel N
FAU - Hamm-Alvarez, Sarah F
AU  - Hamm-Alvarez SF
FAU - McDonough, Alicia A
AU  - McDonough AA
LA  - eng
GR  - DK34316/DK/NIDDK NIH HHS/United States
GR  - DK48522/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Diuretics)
RN  - 0 (Slc9a3 protein, rat)
RN  - 0 (Sodium-Hydrogen Exchanger 3)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 7DZO8EB0Z3 (Amiloride)
SB  - IM
MH  - Amiloride/pharmacology
MH  - Animals
MH  - Biological Transport, Active
MH  - Diuretics/pharmacology
MH  - Fluorescent Antibody Technique, Indirect
MH  - Hemodynamics/physiology
MH  - Hypertension/*physiopathology
MH  - Kidney Tubules, Proximal/drug effects/*enzymology/*physiopathology
MH  - Kinetics
MH  - Male
MH  - Membranes/enzymology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium-Hydrogen Exchanger 3
MH  - Sodium-Hydrogen Exchangers/*metabolism
MH  - Subcellular Fractions/drug effects/metabolism
EDAT- 2002/03/07 10:00
MHDA- 2002/04/20 10:01
CRDT- 2002/03/07 10:00
PHST- 2002/03/07 10:00 [pubmed]
PHST- 2002/04/20 10:01 [medline]
PHST- 2002/03/07 10:00 [entrez]
AID - 10.1152/ajprenal.00298.2001 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2002 Apr;282(4):F730-40. doi: 
      10.1152/ajprenal.00298.2001.