Gadolinium and ruthenium red attenuate remote hind limb preconditioning-induced cardioprotection: possible role of TRP and especially TRPV channels.
Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat. Using Langendorff's system, the heart was perfused and subjected to 30-min ischemia and 120-min reperfusion. The myocardial injury was assessed by measuring infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), LVDP, +dp/dtmax, -dp/dtmin, heart rate, and coronary flow rate. Gadolinium, TRP blocker, and ruthenium red, TRPV channel blocker, were employed as pharmacological tools. Remote hind limb preconditioning significantly reduced the infarct size, LDH release, CK release and improved coronary flow rate, hemodynamic parameters including LVDP, +dp/dtmax, -dp/dtmin, and heart rate. However, gadolinium (7.5 and 15 mg kg(-1)) and ruthenium red (4 and 8 mg kg(-1)) significantly attenuated the cardioprotective effects suggesting the involvement of TRP especially TRPV channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus possibly activates TRPV channels on the heart or sensory nerve fibers innervating the heart to induce cardioprotective effects. Alternatively, remote hind limb preconditioning stimulus may also activate the mechanosensitive TRP and especially TRPV channels on the sensory nerve fibers innervating the skeletal muscles to trigger cardioprotective neurogenic signaling cascade. The cardioprotective effects of remote hind limb preconditioning may be mediated via activation of mechanosensitive TRP and especially TRPV channels.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India.
Puneet Kaur
PK
Randhawa
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India. amteshwarjaggi@yahoo.co.in.
Amteshwar Singh
AS
Jaggi
D000818:Animals; D015415:Biomarkers; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D019194:Ischemic Preconditioning / 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 / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / 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; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D015415:Biomarkers; D049990:Membrane Transport Modulators; D050916:TRPV Cation Channels; D012430:Ruthenium Red; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase
Heart; Mechanosensitive channels; Remote hind limb preconditioning; TRPV channels