title: Cardioprotection by ischemic postconditioning is lost in isolated perfused heart from diabetic rats: Involvement of transient receptor potential vanilloid 1, calcitonin gene-related peptide and substance P.
abstract: We previously found that the expression of transient receptor potential vanilloid 1 (TRPV1) and contents of calcitonin gene-related peptide (CGRP) and substance P (SP), two main neuropeptides released from TRPV1, were decreased in diabetic hearts. This study aimed to test whether decreased TRPV1, CGRP and SP levels were responsible for the loss of cardioprotection by ischemic postconditioning (IPostC) in isolated perfused heart from streptozotocin-induced diabetic rats. IPostC effectively protected non-diabetic hearts against ischemia/reperfusion injury by improving cardiac function and lowering creatine kinase (CK) and cardiac troponin I (cTnI) release, which could be abolished by inhibiting TRPV1, CGRP receptor or SP receptor. However, IPostC had no effect on cardiac function and the release of CK and cTnI in diabetic hearts regardless of whether TRPV1, CGRP receptor or SP receptor were inhibited. CGRP or SP-induced postconditioning significantly prevented both non-diabetic and diabetic hearts from ischemia/reperfusion injury by improving cardiac function and lowering CK and cTnI release. Additionally, IPostC markedly increased CGRP and SP release in non-diabetic hearts, which could be reversed with TRPV1 inhibition, but not CGRP receptor or SP receptor inhibition. However, IPostC failed to affect CGRP and SP release in diabetic hearts in the presence or absence of TRPV1, CGRP receptor or SP receptor inhibition. These results indicate that the loss of cardioprotection by IPostC during diabetes is partly associated with a failure to increase CGRP and SP release, likely due to decreased TRPV1 expression and CGRP and SP contents in diabetic hearts.
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Ren
authors.forename: Jun-Xian
authors.initials: JX
authors.lastname: Song
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin