title: Exploring the Role of TRPV and CGRP in Adenosine Preconditioning and Remote Hind Limb Preconditioning-Induced Cardioprotection in Rats.
abstract: The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released. Four cycles of ischemia and reperfusion, each consisting of 5 min of inflation and 5 min of deflation of pressure cuff were used to produce remote limb preconditioning. An ex vivo Langendorff's isolated rat heart model was used to induce ischemia reperfusion injury by 30 min of global ischemia followed by 120 min of reperfusion. RIPC demonstrated a significant decrease in ischemia reperfusion-induced significant myocardial injury in terms of increase in LDH, CK, infarct size and decrease in LVDP, +dp/dtmaxand -dp/dtmin. Moreover, pharmacological preconditioning with adenosine produced cardioprotective effects in a similar manner to RIPC. Pretreatment with sumatriptan, a CGRP release blocker, abolished RIPC and adenosine preconditioning-induced cardioprotective effects. Administration of ruthenium red, a TRPV inhibitor, also abolished adenosine preconditioning-induced cardioprotection. It may be proposed that the cardioprotective effects of adenosine and remote preconditioning are possibly mediated through activation of a TRPV channels and consequent, release of CGRP.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Amritpal
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Puneet Kaur
authors.initials: PK
authors.lastname: Randhawa
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Anjana
authors.initials: A
authors.lastname: Bali
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India. amteshwarjaggi@yahoo.co.in.
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply*; D019194:Ischemic Preconditioning / Q000379:methods*; D000067268:Isolated Heart Preparation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012430:Ruthenium Red / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018170:Sumatriptan / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D050916:TRPV Cation Channels; D012430:Ruthenium Red; D018170:Sumatriptan; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine
keywords: Adenosine preconditioning; CGRP; Cardioprotection; Remote ischemic preconditioning; Ruthenium red; Sumatriptan; TRPV1 channels