Effects of tramadol hydrochloride pretreatment on expression of calcitonin gene-related peptide in myocardium following acute myocardial ischemia in rats

Abstract

Objective To investigate the effects of tramadol hydrechloride pretreatment on the expression of calcitonin gene-related peptide (CGRP) in ischemic and non-ischemic myocardium following acute myocardial is-chemia in the rats. Method Eighteen adult male SD rats weighing 270 to 300 g were randomly divided into three groups(n = 6, in each): group Ⅰ ,sham operation; group Ⅱ , myocardial isehemia, and group Ⅲ, tramadol hydrochloride pretreatment. The anterior descending branch of left coronary artery was occluded(CAO)for 3 hours in rats of group Ⅱ and Ⅲ. In group Ⅲ, tramadol hydrochloride 12.5 mg·kg~(-1) was injected through caudal vein 15 minutes before CAO. At 3 hours after myocardial ischemia, the hearts were removed for determination of CGRP protein content in ischemic and non-ischemie myocardium by immuno-histochemistry and enzyme immunometric as-say, and the expression of CGRPmRNA by RT-PCR. One-way ANOVA was used for statistical analysis. ResultsOnly β-CGRPmRNA was found in rats myocardium. In the ischemic myocardium, the average light density of CGRP(0.215 ± 0. 100), positive unit (36.95 ± 1.70), concentration (39.06 ± 1.86) and expression of β-CGRP mRNA 0. 946 ± 0. 019) were significantly increased in group Ⅱ compared with those in group Ⅰ (0. 139 ± 0.006), (25.01 ± 1.03), (20.80± 1.24), (0.734±0.025) (P <0.05), and decreased markedly in group Ⅲ(0.158+0.008),(28.53±1.21),(28.58±2.10),(0.872±0.024) (P < 0.05) In the non-ischemic my-ocardium, the average hght density of CGRP(0.156 ± 0.017), positive unit(28.57 ± 2.23), concentration (28.58 ± 1.12) and expression of β-CGRP mRNA(0.810 ± 0.021) were significantly increased in group Ⅱ com-pared with those in group Ⅰ (0.109+0.013, 20.91 ～2.14, 17.35+2.72, 0.701 ～0.018) (P < 0.05), and decreased markedly in group Ⅲ(0.120±0.008), (22.58±1.18), (23.26±2.41), (0.779±0.022) (P < 0.05). Conclusions Tramadol hydrochloride pretreatment can significantly inhibit increase in CGRP expression in myocardium elicited by CAO, which might imply that tramadol hydrochloride might take part in protection of my-ocardium against acute myocardial ischemia by means of pain-relief. Key words: Tramadol Hydrochloride; Pretreatment; Calcitonin gene related pipetide; Myocardial ischemia; Rats