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Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic humans.
MedLine Citation:
PMID:  22859405     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Endothelin-1 inhibits collecting duct sodium reabsorption and stimulates proximal and distal tubule acidification in experimental animals both directly and indirectly via increased mineralocorticoid activity. Dietary-induced acid loads were shown to increase renal endothelin-1 activity and it is hypothesized that increased dietary acid-induced endothelin-1 activity may be a causative progression factor in human renal insufficiency and that this might be reversed by provision of dietary alkali Aims: To clarify, in normal human volunteers, the role of endothelin-1 in renal acidification and to determine whether the effect is dependent on dietary sodium chloride. Methods: Acid-base equilibrium was studied 7 normal human volunteers with experimentally induced metabolic acidosis (NH(4)Cl 2.1 mmols/kg/bw/d) with and without inhibition of endogenous endothelin-1 activity by the endothelin A/B-receptor antagonist bosentan (125 bid p.o./d) both during dietary NaCl restriction (20 mmols/day) and NaCl repletion (2 mmols NaCl/kg bw/d). Results: During NaCl restriction, but not in the NaCl replete state, bosentan significantly increased renal net acid excretion in association with stimulation of ammoniagenesis resulting in a significantly increased plasma bicarbonate concentration (19.0±0.8 to 20.1± 0.9 mmol/L) despite a decrease in mineralocorticoid activity and an increase in endogenous acid production. Conclusions: In pre-existing human metabolic acidosis, endothelin-1 activity worsens acidosis by decreasing the set-point for renal regulation of plasma bicarbonate concentration, but only when dietary NaCl provision is restricted..
Authors:
Alexandra Pallini; Henry Nicolas Hulter; Jurgen Muser; Reto Krapf
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-1
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  -     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Kantonsspital Bruderholz.
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