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

Abstract
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 (KATP) 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 KATP 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 KATP channel opening. We conclude that natriuretic peptide/cGMP/KATPchannel signaling may constitute an important injury-limiting mechanism in myocardium.