B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening

Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1592-600. doi: 10.1152/ajpheart.00902.2002. Epub 2003 Jan 9.


B-type natriuretic peptide (BNP) has been reported to be released from the myocardium during ischemia. We hypothesized that BNP mediates cardioprotection during ischemia-reperfusion and examined whether exogenous BNP limits myocardial infarction and the potential role of ATP-sensitive potassium (K(ATP)) channel opening. Langendorff-perfused rat hearts underwent 35 min of left coronary artery occlusion and 120 min of reperfusion. The control infarct-to-risk ratio was 44.8 +/- 4.4% (means +/- SE). BNP perfused 10 min before ischemia limited infarct size in a concentration-dependent manner, with maximal protection observed at 10(-8) M (infarct-to-risk ratio: 20.1 +/- 5.2%, P < 0.01 vs. control), associated with a 2.5-fold elevation of myocardial cGMP above the control value. To examine the role of K(ATP) channel opening, glibenclamide (10(-6) M), 5-hydroxydecanoate (5-HD; 10(-4) M), or HMR-1098 (10(-5) M) was coperfused with BNP (10(-8) M). Protection afforded by BNP was abolished by glibenclamide or 5-HD but not by HMR-1098, suggesting the involvement of putative mitochondrial but not sarcolemmal K(ATP) channel opening. We conclude that natriuretic peptide/cGMP/K(ATP) channel signaling may constitute an important injury-limiting mechanism in myocardium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / metabolism
  • Atrial Natriuretic Factor / pharmacology*
  • Cardiotonic Agents / metabolism
  • Cardiotonic Agents / pharmacology*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / pharmacology
  • Dose-Response Relationship, Drug
  • Heart Ventricles / metabolism
  • Ion Channel Gating / drug effects
  • Ischemic Preconditioning, Myocardial
  • Male
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / pathology
  • Myocardium / metabolism
  • Natriuretic Peptide, Brain
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Cardiotonic Agents
  • Potassium Channel Blockers
  • Potassium Channels
  • Natriuretic Peptide, Brain
  • 8-bromocyclic GMP
  • Atrial Natriuretic Factor
  • Cyclic GMP