B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening.
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.
D'Souza
Savio P
SP
The Hatter Institute, University College London Hospitals and Medical School, London WC1E 6BT, United Kingdom.
Yellon
Derek M
DM
Martin
Claus
C
Schulz
Rainer
R
Heusch
Gerd
G
Onody
Annamaria
A
Ferdinandy
Peter
P
Baxter
Gary F
GF
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D020097:Natriuretic Peptide, Brain; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP