Role of calcitonin gene-related peptide in myocardial ischemic preconditioning and its relation with ATP-sensitive K＋ channel in intact rats

doi:10.3321/j.issn:1673-4254.2001.01.010

Abstract：Objective The aim of this study was to investigate whethercalcitonin gene-related peptide (CGRP) plays a role in ischemic preconditioning (IPC) in an intact rat model. Methods Ninety-six SD rats were randomly divided into 8 groups, all of whom were subjected to 30-min regional ischemic followed by 2-h reperfusion, after preconditioning disposal. The IPC protocol consisted of 3 cycles of 5-min regional ischemia and 3 cycles of 5-min reperfusion. The preconditioning disposal for different groups were as the following: CGRP (10 μg/kg.b.w.) was given 20 min before 30-min ischemia (CGRP group); glibenclamide (GLI) was given 30 min before CGRP (GLI+CGRP group) or IPC (GLI+ICP group); CGRP polyclonal antibody (PcAb, 2.5mg/kg) was given 20 min before first ischemic insult (PcAb group). Plasma CGRP level was determined by radioimmunoassay (RIA), and the infarct size by nitro blue tetrazolium, expressed as percentage of the area at risk. Results Compared with control group, the mean plasma CGRP level at the end of first and especially the third ischemic insult was markedly increased in IPC group (P<0.01), and obvious reduction of the infarct size and declined incidence of ventricular arrhythmia during 30-min ischemia and the subsequent 2-h reperfusion were noted. These effects, however, were attenuated by pretreatment with CGRP PcAb. Pretreatment with CGRP also resulted in the reduction of the infarct size and inhibition of ventricular arrhythmia, only not so obvious as ICP did. GLI pretreatment completely abolished the infarct-limiting effect of CGRP or IPC, but did not affect there antiarrhythmic effects. Conclusion As an endogenous myocardial protective substance, CGRP may play an important role in IPC, and its infarct-limiting effect was probably mediated by ATP-sensitive K+ channel.