Document Detail


Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic humans.
MedLine Citation:
PMID:  22859405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. Diet-induced acid loads have been 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. We sought 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. Acid-base equilibrium was studied in seven normal human volunteers with experimentally induced metabolic acidosis [NH(4)Cl 2.1 mmol·kg body weight (BW)(-1)·day(-1)] with and without inhibition of endogenous endothelin-1 activity by the endothelin A/B-receptor antagonist bosentan (125 BID p.o./day) both during dietary NaCl restriction (20 mmol/day) and NaCl repletion (2 mmol NaCl·kg BW(-1)·day(-1)). 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. 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 N Hulter; Jurgen Muser; Reto Krapf
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Publication Detail:
Type:  Journal Article     Date:  2012-08-01
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  303     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-01-11     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F991-9     Citation Subset:  IM    
Affiliation:
Univ. Dept. of Medicine, Kantonsspital Bruderholz, CH-4101 Bruderholz/Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Acid-Base Equilibrium / drug effects,  physiology*
Acidosis / chemically induced,  metabolism*
Adult
Diet
Endothelin-1 / metabolism*
Homeostasis / drug effects
Humans
Kidney / drug effects,  metabolism*
Male
Receptors, Endothelin / antagonists & inhibitors
Sodium Chloride, Dietary / metabolism*
Sulfonamides / pharmacology
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Receptors, Endothelin; 0/Sodium Chloride, Dietary; 0/Sulfonamides; Q326023R30/bosentan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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