title: Investigating the involvement of TRPV1ion channels in remote hind limb preconditioning-induced cardioprotection in rats.
abstract: Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat. The Langendorff system was used to perfuse the isolated heart and afterward was subjected to 30 min of global ischemia and 120 min of reperfusion. Sustained ischemia and, thereafter, reperfusion led to cardiac injury that was assessed in terms of infarct size, lactate dehydrogenase (LDH) release, creatine kinase (CK) release, left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), +dp/dtmax, -dp/dtmin,heart rate, rate pressure product, and coronary flow rate. The pharmacological modulators employed included capsaicin as TRPV1agonist and capsazepine as TRPV1antagonist. Remote hind limb preconditioning stimulus and capsaicin preconditioning (5 and 10 mg/kg) led to significant reduction in infarct size, LVEDP, LDH release, CK release, and significant improvement in LVDP, +dp/dtmax, -dp/dtmin, heart rate, rate pressure product, and coronary flow rate. However, remote hind limb preconditioning-induced cardioprotective effects were considerably abolished in the presence of capsazepine (2.5 and 5 mg/kg). This indicates that remote hind limb preconditioning stimulus possibly activates TRPV1channels to produce cardioprotective effects.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, 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, 147002, India. amteshwarjaggi@yahoo.co.in.
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006339:Heart Rate; D006614:Hindlimb / Q000098:blood supply*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D000067268:Isolated Heart Preparation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000494:pharmacology; 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; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D049990:Membrane Transport Modulators; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; C071423:capsazepine; D002211:Capsaicin
keywords: Cardioprotection; Ischemia; Remote preconditioning; TRPV1 channels