Abstract
In order to explore whether monophosphoryl lipid A (MLA)-induced delayed cadioprotection is mediated by calcitonin gene-related peptide (CGRP) and the regulatory effect of inducible heme oxygenase isorform (HO-1)/carbon monoxide (CO) on CGRP synthesis and release, the expression of CGRP and HO-1 in dorsal root ganglia (DRG) and CGRP concentration in plasma were determined in rats. Pretreatment with MLA (500 microg/kg, i.p.) significantly reduced infarct size and creatine kinase release after the 45-min coronary artery occlusion and 180-min reperfusion. MLA caused a significant increase in the expression of CGRP and HO-1 and plasma concentrations of CGRP. The cardioprotection as well as the synthesis and release of CGRP induced by MLA were completely abolished by pretreatment with zinc protoporphrin IX (ZnPP-9), an inhibitor of HO-1, or by capsaicin (50 mg/kg, s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves. Pretreatment with Znpp-9 had no effect on HO-1 expression, but capsaicin abrogated the expression of HO-1 induced by MLA in DRG. These results suggest that the delayed cardioprotection afforded by MLA is mediated by CGRP via activation of the HO-1 pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / pharmacology*
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Animals
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Calcitonin Gene-Related Peptide / antagonists & inhibitors
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Calcitonin Gene-Related Peptide / blood
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Calcitonin Gene-Related Peptide / genetics
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Calcitonin Gene-Related Peptide / metabolism*
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Capsaicin / pharmacology
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Carbon Monoxide / blood
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Cardiotonic Agents / administration & dosage
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Cardiotonic Agents / pharmacology*
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Creatine Kinase / blood
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Ganglia, Spinal / drug effects
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Heme Oxygenase (Decyclizing) / metabolism*
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Heme Oxygenase-1
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Injections, Intraperitoneal
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Ischemic Preconditioning, Myocardial
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Lipid A / administration & dosage
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Lipid A / analogs & derivatives*
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Lipid A / pharmacology*
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Male
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Myocardial Infarction / pathology
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Myocardium / metabolism
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Protoporphyrins / pharmacology
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Reperfusion Injury / metabolism
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Reperfusion Injury / pathology
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Reperfusion Injury / prevention & control*
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Signal Transduction
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Time Factors
Substances
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Adjuvants, Immunologic
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Cardiotonic Agents
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Lipid A
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Protoporphyrins
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RNA, Messenger
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zinc protoporphyrin
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Carbon Monoxide
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1
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Creatine Kinase
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Calcitonin Gene-Related Peptide
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monophosphoryl lipid A
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Capsaicin