Adaptation of nhe-3 in the rat thick ascending limb : effects of
high sodium intake and metabolic alkalosis..
Laghmani, Kamel, R[acute]egine Chambrey, Marc Froissart, Maurice
Bichara, Michel Paillard, and Pascale Borensztein.
Laboratoire de Physiologie et Endocrinologie Cellulaire
R[acute]enale, Institut National de la Sant[acute]e et de la
Recherche M[acute]edicale U. 356, Universit[acute]e Pierre et Marie
Curie, Centre Hospitalo-Universitaire Broussais, Paris, France.
APStracts 5:0164F, 1998.
The present studies examined the effects of chronic NaCl
administration and metabolic alkalosis on NHE-3, an apical Na/H
exchanger of the rat medullary thick ascending limb of Henle (MTAL).
NaCl administration had no effect on NHE-3 mRNA abundance as assessed
by competitive RT-PCR, and on NHE-3 transport activity estimated from
the Na-dependent cell pH recovery of Na-depleted acidified MTAL
cells, in the presence of 50_M HOE694 which specifically blocks NHE-1
and NHE-2. Two models of metabolic akalosis were studied, one
associated with high sodium intake i.e., NaHCO3 administration, and
one not associated with high sodium intake, i.e., chloride depletion
alkalosis (CDA). In both cases, the treatment induced a significant
metabolic alkalosis which was associated with a decrease in NHE-3
transport activity (-27 % and -25 %, respectively). Negative linear
relationships were observed between NHE-3 activity and plasma pH or
bicarbonate concentration. NHE-3 mRNA abundance, and NHE-3 protein
abundance, assessed by Western-blot analysis, also decreased by
respectively 35 and 25 % during NaHCO3-induced alkalosis, and by 47
and 33 % during CDA. These studies demonstrate that high sodium
intake has per se no effect on MTAL NHE-3. In contrast, chronic
metabolic alkalosis associated or not with high sodium intake leads
to an appropriate adaptation of NHE-3 activity, which involves a
decrease in NHE-3 protein and mRNA abundance.
Received 23 February 1998; accepted in final form 10 September
1998.
APS Manuscript Number F42-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 October 1998