Role of TRPV1/CGRP signaling pathway in lidocaine postconditioning-induced reduction of myocardial ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the role of transient receptor potential vanillic acid subtype 1(TRPV1)/calcitonin gene-related peptide(CGRP) signaling pathway in lidocaine postconditioning-induced reduction of myocardial ischemia-reperfusion(I/R) injury in rats. Methods Forty healthy male Sprague-Dawley rats, aged 3 months, weighing 250-300 g, were divided into 5 groups(n=8 each) using a random number table method: sham operation group(group Sham), group I/R, lidocaine postconditioning group(group LP), lidocaine postconditioning plus CGRP8-37 group(group LP+ CGRP8-37), and lidocaine postconditioning plus capsazepine group(group LP+ Capz). Myocardial ischemia was induced by ligating the anterior descending branch of left coronary artery for 30 min, followed by 120-min reperfusion in anesthetized rats. Lidocaine 2 mg/kg was injected via the tail vein at 5 min before reperfusion in group LP. In group LP + CGRP8-37, lidocaine was intravenously injected, and CGRP receptor selective antagonist CGRP8-37 2 mg/kg was intravenously injected at the same time. In group LP+ Capz, lidocaine was injected intravenously, and TRPV1 blocker capsazepine 3 mg/kg was injected intravenously at the same time. A catheter was retrogradely implanted to the left ventricle, and heart rate(HR), left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVEDP), and the maximum rate of increase or decrease in left ventricular pressure(±dp/dtmax) were continuously monitored and recorded. Blood samples were collected from the carotid artery at 120 min of reperfusion for determination of cardiac troponin I(cTnI), myoglobin(Myo) and creatine kinase-MB(CK-MB) concentrations in serum. Rats were then sacrificed for determination of myocardial infarct size. Results Compared with Sham group, the serum concentrations of cTnI, Myo and CK-MB were significantly increased, LVSP, + dP/dtmax and HR were decreased, and LVEDP and -dP/dtmax were increased in I/R group and LP group(P 0.05). Compared with group LP, the serum concentrations of cTnI and Myo, myocardial infarct size and LVEDP were significantly increased, and + dP/dtmax was decreased in group LP+ CGRP8-37, and the serum concentrations of cTnI and Myo and myocardial infarct size were significantly increased, LVSP and + dP/dtmax were decreased, and LVEDP was increased in group I/R+ Lido+ Capz(P<0.05). Conclusion The mechanism by which lidocaine postconditioning mitigates myocardial I/R injury is related to activating TRPV1/CGRP signaling pathway in rats. Key words: Lidocaine; Ischemia postconditioning; Myocardial reperfusion injury; Calcitonin gene-related peptide; TRPV cation channels