Calcitonin gene related peptide mediates cardioprotection by remote preconditioning
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Calcitonin gene related peptide mediates cardioprotection by remote preconditioning. / Wolfrum, Sebastian; Nienstedt, Julie; Heidbreder, Marc; Schneider, Kathrin; Dominiak, Peter; Dendorfer, Andreas.
In: REGUL PEPTIDES, Vol. 127, No. 1-3, 15.04.2005, p. 217-24.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Calcitonin gene related peptide mediates cardioprotection by remote preconditioning
AU - Wolfrum, Sebastian
AU - Nienstedt, Julie
AU - Heidbreder, Marc
AU - Schneider, Kathrin
AU - Dominiak, Peter
AU - Dendorfer, Andreas
PY - 2005/4/15
Y1 - 2005/4/15
N2 - Excitation of sensory nerves and activation of myocardial protein kinase C (PKC) epsilon contribute to the transduction of remote preconditioning (RPC) to the heart. Since calcitonin gene related peptide (CGRP) is an important mediator of sensory neurons we tried to delineate whether CGRP a) protects the heart from ischemic injury, b) is involved in cardioprotection after RPC, and c) leads to an activation of myocardial PKCepsilon. RPC was achieved by brief mesenteric artery occlusion followed by reperfusion. Myocardial infarct size (IS) was measured by TTC staining after temporary coronary artery occlusion (CAO) in rats. CGRP plasma levels were determined by radioimmunoassay and PKCepsilon was measured by quantitative immunoblotting. CGRP infusion reduced infarct size by 57%, an action that was abolished after co-treatment with the PKC inhibitor chelerythrine. RPC significantly increased CGRP plasma levels, reduced infarct size, and activated myocardial PKCepsilon. Infarct size reduction was abolished and PKCepsilon activation was significantly attenuated by CGRP(8-37), a specific CGRP receptor antagonist. Ganglion blockade with hexamethonium did not influence CGRP release by RPC but abolished CGRP mediated myocardial PKCepsilon activation. In conclusion, CGRP protects the heart from ischemic injury and is involved in RPC, presumably by activating myocardial PKCepsilon.
AB - Excitation of sensory nerves and activation of myocardial protein kinase C (PKC) epsilon contribute to the transduction of remote preconditioning (RPC) to the heart. Since calcitonin gene related peptide (CGRP) is an important mediator of sensory neurons we tried to delineate whether CGRP a) protects the heart from ischemic injury, b) is involved in cardioprotection after RPC, and c) leads to an activation of myocardial PKCepsilon. RPC was achieved by brief mesenteric artery occlusion followed by reperfusion. Myocardial infarct size (IS) was measured by TTC staining after temporary coronary artery occlusion (CAO) in rats. CGRP plasma levels were determined by radioimmunoassay and PKCepsilon was measured by quantitative immunoblotting. CGRP infusion reduced infarct size by 57%, an action that was abolished after co-treatment with the PKC inhibitor chelerythrine. RPC significantly increased CGRP plasma levels, reduced infarct size, and activated myocardial PKCepsilon. Infarct size reduction was abolished and PKCepsilon activation was significantly attenuated by CGRP(8-37), a specific CGRP receptor antagonist. Ganglion blockade with hexamethonium did not influence CGRP release by RPC but abolished CGRP mediated myocardial PKCepsilon activation. In conclusion, CGRP protects the heart from ischemic injury and is involved in RPC, presumably by activating myocardial PKCepsilon.
KW - Animals
KW - Blood Pressure
KW - Calcitonin Gene-Related Peptide
KW - Cardiotonic Agents
KW - Dose-Response Relationship, Drug
KW - Enzyme Activation
KW - Heart
KW - Ischemic Preconditioning, Myocardial
KW - Male
KW - Myocardial Infarction
KW - Myocardial Ischemia
KW - Neurons, Afferent
KW - Protein Kinase C
KW - Protein Kinase C-epsilon
KW - Random Allocation
KW - Rats
KW - Rats, Wistar
KW - Journal Article
U2 - 10.1016/j.regpep.2004.12.008
DO - 10.1016/j.regpep.2004.12.008
M3 - SCORING: Journal article
C2 - 15680490
VL - 127
SP - 217
EP - 224
JO - REGUL PEPTIDES
JF - REGUL PEPTIDES
SN - 0167-0115
IS - 1-3
ER -