title: The modulating actions of sulfonylurea on atrial natriuretic peptide release in experimental acute heart failure.
abstract: OBJECTIVE
  This study defined the modulating actions of sulfonylurea on acute release of atrial natriuretic peptide (ANP) in experimental acute heart failure.
  
  
  BACKGROUND
  Sulfonylurea drugs, blockers of cardioprotective ATP-sensitive K(+) (K(ATP)) channels, may increase the risk of early cardiovascular mortality. In cardiovascular diseases such as acute heart failure, early release of ANP is essential for cardiorenal homeostasis. Although K(ATP) channels regulate secretion of hormones, such as insulin, it is unknown whether sulfonylureas interfere with ANP release in acute heart failure.
  
  
  METHODS
  The effects of acute administration of glyburide (0.3 mg/kg), a prototype sulfonylurea, on ANP release and sodium excretion were measured in vivo in a canine model of pacing-induced acute heart failure characterized by acute atrial stretch. Immunoreactivity, in atrial tissue, for ANP and the K(ATP) channel subunit, Kir6.2, was determined using specific antibodies.
  
  
  RESULTS
  With increased left atrial pressure in heart failure, plasma levels of ANP increased rapidly and peaked within 25+/-3 min. Glyburide delayed the time required for peak plasma ANP secretion to 48+/-5 min. This resulted in reduced natriuresis from 84+/-17 microEq/min in the absence of glyburide, to 34+/-9 microEq/min in the presence of glyburide. However, glyburide did not alter the renal natriuretic responsiveness to exogenously administered ANP in normal dogs. In atrial tissue, both ANP and the K(ATP) channel subunit, Kir6.2, displayed strong immunoreactivity and co-localization.
  
  
  CONCLUSIONS
  Glyburide delays release of ANP in acute heart failure resulting in impaired natriuresis. This cannot be ascribed to an antinatriuretic effect on the kidney, but rather may be due to interference with K(ATP) channel-dependent ANP secretion from the atrium. Such adverse outcome of sulfonylurea drug use could reduce the compensatory capacity to preserve cardiorenal homeostasis in acute heart failure.
authors.affiliation: Cardiorenal and Cardiovascular Research Laboratories, Division of Cardiovascular Diseases, Departments of Medicine, Physiology and Pharmacology, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA. chen.horng@mayo.edu
authors.forename: H H
authors.initials: HH
authors.lastname: Chen
authors.forename: K Y
authors.initials: KY
authors.lastname: Oh
authors.forename: A
authors.initials: A
authors.lastname: Terzic
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D004285:Dogs; D005905:Glyburide / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects*; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D009318:Natriuresis / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D015221:Potassium Channels; D009320:Atrial Natriuretic Factor; D005905:Glyburide