title: Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia.
abstract: BACKGROUND
  Angiotensin II stimulates the proximal tubular Na/H antiporter and increases proximal tubular cell pH. Because intracellular pH may affect urinary citrate excretion and enzymes responsible for renal citrate metabolism, the present studies examined the effect of enalapril, an angiotensin converting enzyme inhibitor, on the activity of renal cortical ATP citrate lyase and urinary citrate excretion.
  
  
  METHODS
  Enalapril was given to rats (15 mg/kg/day) for seven days and to humans (10 mg twice daily) for 10 days. Blood and 24-hour urine samples were obtained in both groups. Renal cortical tissue from rats was analyzed for enzyme activity.
  
  
  RESULTS
  In rats, enalapril decreased urinary citrate excretion by 88%. The change in urinary citrate was not associated with a difference in plasma pH, bicarbonate nor potassium concentration. However, similar to metabolic acidosis and hypokalemia, enalapril caused a 42% increase in renal cortical ATP citrate lyase activity. When given to humans, enalapril significantly decreased urinary citrate excretion and urine citrate concentration by 12% and 16%, respectively, without affecting plasma pH or electrolytes.
  
  
  CONCLUSIONS
  Enalapril decreases urinary citrate in rats and humans. This is due, at least in part, to increases in cytosolic citrate metabolism through ATP citrate lyase in rats similar to that seen with chronic metabolic acidosis and hypokalemia. The effects of enalapril on urinary citrate and renal cortical ATP citrate lyase occur independently of acidosis or hypokalemia but may be due to intracellular acidosis that is common to all three conditions.
authors.affiliation: Departments of Internal Medicine, Mineral Metabolism and Pediatrics, University of Texas, Southwestern Medical Center, Dallas, Texas, USA. j-melnick@nwu.edu
authors.forename: J Z
authors.initials: JZ
authors.lastname: Melnick
authors.forename: P A
authors.initials: PA
authors.lastname: Preisig
authors.forename: S
authors.initials: S
authors.lastname: Haynes
authors.forename: C Y
authors.initials: CY
authors.lastname: Pak
authors.forename: K
authors.initials: K
authors.lastname: Sakhaee
authors.forename: R J
authors.initials: RJ
authors.lastname: Alpern
mesh_terms: D000138:Acidosis / Q000652:urine*; D000328:Adult; D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D019343:Citric Acid / Q000652:urine*; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000652:urine*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D019343:Citric Acid; D004656:Enalapril