| Objective:The aim of the study was to investigate effects of calcitonin gene-related peptide(CGRP) on cardiac function and electrophysiology of isolated perfuded rat Hearts.The effects of CGRP on norepinephrine(NE)induced cardiac positive inotropic and chronotropic action and arrhythmia and its primary mechanism were studied.METHODS:Isolated normal SD rat hearts were perfused with a Langendorff apparatus.The experiments were carried out in three groups,i.e.,CGRP group,NE group and CGRP+NE group.A range of doses of 10-6M-10-8M of CGRP and 10-4M-10-7M of NE were used to investigate the dose response relationship for the effects of CGRP and NE groups on the heart respectively.Then the effects of CGRP on NE-induced action on the heart were studied on the isolated hearts in CGRP+NE group.RESULTS:CGRP at the doses of 10-7M and 10-8M enhanced cardiac function and exerted positive effects on left ventricular developed pressure(LVDP,i.e.,left ventricular systolic pressure-left ventricular end-diastolic pressure(LVSP-LVEDP),while decreases LVEDP. CGRP caused significant increase in heart rate(P＜0.05).The enhancement effects of CGRP on LVDP and heart rate were in a dose-dependent manner.CGRP at the dose of 10-7M decreased LVEDP significantly compared to the control(P＜0.05).CGRP at lower concentration of 10-8M also caused decrease in LVEDP but the change was not significantly different from the control (P＞0.05).The lagest dose of CGRP(10-6M)used in this study did not produce any significant effect on LVDP and heart rate(P＞0.05).However,it could increase LVEDP to a higher level when compared to the control(P＜0.05).NE at the doses of 10-4M-10-7M significantly produced positive effects on LVDP and heart rate(P＜0.05).NE at the dose of 10-4M and 10-5M decreased LVEDP significantly compared to the control(P＜0.05),but NE at the dose of 10-6M and 10-7M failed to produce significant effect on LVEDP(P＞0.05).In group of CGRP+NE,when CGRP was used with NE simultaneously(10-8M of CGRP+ 10-5M of NE),LVEDP was increased to a level greater than the effect produced by NE (10-5M)alone(P＜0.05).But the heart rate was lower compared with the result obtained with NE(10-5M)alone(P＜0.05).While there was no statistical difference in LVEDP between two groups(CGRP+NE and NE groups).There was no significant difference in morbidity of arrhythmia between CGRP and control groups(P＞0.05).NE at the dose of 10-5M could induce serious arrhythmia(P＜0.05),mainly premature ventricular rates.The morbidity of premature ventricular rate could reach 11.7BPM. The other doses of NE including 10-7M,10-6M,and 10-4M showed no difference in morbidity of arrhythmia when compared with the control(P＞0.05).There was a reduction of the morbidity of arrhythmia in CGRP+NE group compared with the result from NE group.There was no statistic difference in the morbidity of arrhythmia between C8N5 group and control group(P＞0.05).CONCLUSION:CGRP at doses of 10-7M and 10-8M produced positive inotropic action and positive chronotropic action in normal isolated heart of rat and the effect increased with doses. The differential effects of CGRP on NE induced action on heart were observed in this study. CGRP at dose of 10-8M could enhance NE-induced positive inotropic action,but attenuate NE-induced positive chronotropic action.CGRP produced significant anti-arrhythmic effects on NE induced ventricular arrhythmia.
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