The Changes Of SP And CGRP In Rat's Myocardium Following The Coronary Artery Occlusion And The Intervention Effects Of Morphine And Tramadol

Objective To investigate the role of Neurogenic mechanism and the mechanism of cardioprotection of pain-intervene during acute myocardial ischemia the observation was made on the changes in substance P (SP) and calcitonin gene-related peptide (CGRP) in the ischemic and the non-ischemic myocardium induced by coronary artery occlusion (CAO) in rats. Methods (1) Twenty-four adult male Sprague-Dawley rats, weighing 270-300g were randomized assigned to four groups: Control group; CAO1h group; CAO3h group; CAO6h group. The left anterior descending coronary artery was occluded(CAO) except for Control group. The hearts were excised as scheduled and processed for SP and CGRP immunohistochemistry(IHC) and for SPmRNA and CGRPmRNA Semi-quantitative RT-PCR examination. (2) Twenty-four adult male Sprague-Dawley rats, weighing 270-300g were randomly divided into four groups: Control group,Ischemia group,Morphine group and Tramadol group. The left anterior descending coronary artery was occluded (CAO) except for Control group for 3 hours. The rats were pre-administrated 1.25mg.kg-1 Morphine in Morphine group and 1.25mg.kg-1 Tramadol in Tramadol group through caudal vein 15min before CAO. The hearts was excised as scheduled and processed for SP and CGRP immunohistochemistry(IHC) and Enzyme Immunometric Assay(EIA) and for SPmRNA and CGRPmRNA Semi-quantitative RT-PCR examination. Results (1) SP and SPmRNA levels in myocardium of ischemic areas and myocardium of non-ischemic areas and SPmRNA levels in dorsal root ganglion(DRG) were significantly elevated after CAO when compared with control group and peaked in rats of CAO3h group; In the myocardium of non-ischemic areas, SP and SPmRNA levels were less than those in myocardium of ischemic areas in CAO groups. (2) Only β-CGRPmRNA was detected in rat's myocardium, but α-CGRPmRNA and β-CGRPmRNA were detected in rat's DRG. CGRP levels in myocardium and α-CGRPmRNA and β-CGRPmRNA in DRG levels were significantly elevated after CAO when compared with control group and peaked in CAO3h group, but β-CGRPmRNA in myocardium only were significantly elevated after CAO3h and CAO6h; In myocardium of non-ischemic areas, CGRP and β-CGRPmRNA levels were less than those in myocardium of ischemic areas in CAO groups. (3) Both SP/SPmRNA and CGRP/β-CGRPmRNA levels in myocardium of ischemic areas and SPmRNA,α-CGRPmRNA and β-CGRPmRNA levels in DRG were elevated significantly in ischemia group compared with control group and decreased markedly in Morphine group and Tramadol group. In myocardium of nonischemic areas, the changes were roughly similar with ischemic areas, but both SP/SPmRNA and CGRP/β-CGRPmRNA levels were less than those in myocardium of ischemic areas in CAO groups. Conclusion (1) The CAO could evoke the increase on SP and CGRP in rat's whole myocardium and SPmRNA,α-CGRPmRNA and β-CGRPmRNA expression in DRG , which might imply that neurogenic mechanism participate in the pathophysiological changes of myocardial ischemia. (2) Morphine and Tramadol pre-administrated could weaken levels of SP and CGRP in rat's whole myocardium and SPmRNA,α-CGRPmRNA and β-CGRPmRNA expression in DRG evoked by the CAO, which might imply that Morphine and Tramadol pain-intervene might take part in cardioprotection during acute myocardial ischemia.