D'Souza, SP; Yellon, DM; Martin, C; Schulz, R; Heusch, G; Onody, A; ... Baxter, GF; + view all D'Souza, SP; Yellon, DM; Martin, C; Schulz, R; Heusch, G; Onody, A; Ferdinandy, P; Baxter, GF; - view fewer (2003) B-type natriuretic peptide limits infarct size in rat isolated hearts via K-ATP channel opening. AM J PHYSIOL-HEART C , 284 (5) H1592 - H1600. 10.1152/ajpheart.00902.2002.
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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.
|Title:||B-type natriuretic peptide limits infarct size in rat isolated hearts via K-ATP channel opening|
|Keywords:||cGMP, ischemia-reperfusion, infarct size, preconditioning, PROTEIN-KINASE-G, NITRIC-OXIDE, SIGNAL-TRANSDUCTION, GUANYLYL CYCLASES, CORONARY, ACTIVATION, ISCHEMIA, CGMP, MITOCHONDRIAL, SULFONYLUREA|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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