The heme oxygenase-1 pathway is involved in calcitonin gene-related peptide-mediated delayed cardioprotection induced by monophosphoryl lipid A in rats.
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.
Peng
Jun
J
Department of Pharmacology, Xiang-Ya Medical College, Central South University, Hunan 410078, Changsha, China.
Lu
Rong
R
Ye
Feng
F
Deng
Han Wu
HW
Li
Yuan Jian
YJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002248:Carbon Monoxide / Q000097:blood; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D005727:Ganglia, Spinal / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007274:Injections, Intraperitoneal; D019157:Ischemic Preconditioning, Myocardial; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D013997:Time Factors
D000276:Adjuvants, Immunologic; D002316:Cardiotonic Agents; D008050:Lipid A; D011524:Protoporphyrins; D012333:RNA, Messenger; C017803:zinc protoporphyrin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide; C048436:monophosphoryl lipid A; D002211:Capsaicin