Abstract
B-type natriuretic peptide (BNP) has been reported to be released from me 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/KATP channel signaling may constitute an important injury-limiting mechanism in myocardium.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 284 |
| Issue number | 5 53-5 |
| Publication status | Published - May 1 2003 |
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Keywords
- cGMP
- Infarct size
- Ischemia-reperfusion
- Preconditioning
ASJC Scopus subject areas
- Physiology
Cite this
B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening. / D'Souza, Savio P.; Yellon, Derek M.; Martin, Claus; Schulz, Rainer; Heusch, Gerd; Onody, Annamaria; Ferdinándy, P.; Baxter, Gary F.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 5 53-5, 01.05.2003.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening
AU - D'Souza, Savio P.
AU - Yellon, Derek M.
AU - Martin, Claus
AU - Schulz, Rainer
AU - Heusch, Gerd
AU - Onody, Annamaria
AU - Ferdinándy, P.
AU - Baxter, Gary F.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - B-type natriuretic peptide (BNP) has been reported to be released from me 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/KATP channel signaling may constitute an important injury-limiting mechanism in myocardium.
AB - B-type natriuretic peptide (BNP) has been reported to be released from me 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/KATP channel signaling may constitute an important injury-limiting mechanism in myocardium.
KW - cGMP
KW - Infarct size
KW - Ischemia-reperfusion
KW - Preconditioning
UR - http://www.scopus.com/inward/record.url?scp=0037405193&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037405193&partnerID=8YFLogxK
M3 - Article
C2 - 12521930
AN - SCOPUS:0037405193
VL - 284
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 5 53-5
ER -