| Objective:The aim of this study was to investigate the effects of Substance P(SP) on cardiac function and electrophysiology of isolated rat heart.The effects of SP on norepinephrine(NE) induced changes in cardiac function and the primary mechanism were studied.Methods:The study was carried out in 3 steps:1.The study on the effects SP(10-6 mol·L-1,10-7 mol·L-1,10-8 mol·L-1) on cardiac function and electrophysiology of isolated rat heart was performed;2.The effects NE(10-5 mol·L-1,10-6 mol·L-1,10-7 mol·L-1) on cardiac function and electrophysiology of isolated rat heart were investigated;3.The effects of SP on NE induced changes in cardiac function and electrophysiology of isolated rat heart were investigated.After using NK-1 receptor antagonist,[D-Arg1,D-Phe5, D-Trp7,9,Leu11]-Substance P,the effects SP on NE induced changes in cardiac function and electrophysiology of isolated rat heart were examined.The male SD rats(weighing 250-280g) were perfused with a Langendorff apparatus and changes of cardiac function parameters including left ventricular systolic pressure(LVSP),left ventricular end-diastrolic pressure(LVEDP),left ventricular developed pressure(LVDP= LVSP-LVEDP),heart rate(HR) and incidence rate of arrhythmia were investigated.Results:1.There was no significant difference in cardiac function parameters beween SP and the control groups(P＞0.05);2.NE significantly enhanced LVDP,LVSP and HR compared to the control(P＜0.01),The peaked effect was observed in 10-5 mol·L-1NE(N5) group.NE at the dose of 10-5 mol·L-1 decreased LVEDP significantly(P＜0.01),but 10-6 mol·L-1NE(N6) and 10-7 mol·L-1NE(N7) did not show significant effect on LVEDP(P＞0.05);3.Compared with N5 group,LVDP and LVSP was higher and HR was lower in 10-8 mol·L-1 of SP+10-5 mol·L-1 NE(S8N5)group(P＜0.01).There was no significantly difference in LVEDP betweenof S8N5 and N5 groups(P＞0.05).4.HR was lower in 10-7 mol·L-1 of[D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P+10-8 mol·L-1 of SP+10-5 mol·L-1 of NE(D7S8N5)group(P＜0.01),while there was no significantly difference in LVDP,LVSP and LVEDP between D7S8N5 and N5 groups(P＞0.05).In S8N5 group, LVDP and LVSP were significantly higher than in D7S8N5 group(P＜0.01),but there was no significantly difference in LVEDP and HR between D7S8N5 and S8N5 groups(P＞0.05).5.There was no significant difference in incidence of arrhythmia between SP and control groups(P＞0.05).NE at the dose of 10-5 mol·L-1 could induce serious arrhythmia(P＜0.01),while N6 and N7 showed no differdnce in incidence rate of arrhythmia compared with the control (P＞0.05).Compared with N5 group,the incidence rate of arrhythmia was decreased in S8N5 group(P＜0.05).There was no difference in incidence rate of arrhythmia between S8N5 and control group(P＞0.05).Compared with N5 group,incidence rate of arrhythmia was lower in D7S8N5 group(P＜0.05),while there was no significantly difference in D7S8N5,S8N5 and control groups(P＞0.05).Conclusions:There was no any obvious effect of SP at the range of doses,when the SP was used alone,in this study.However,SP could enhance NE-induced positive inotropic effect and decreased NE-induced positive chronotropic effect.NK-1 receptor possibly mediates the effect of SP on NE induced changes in cardiac function of isolated rat heart.
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