Effects Of Substance P On Norepinephrine-induced Ventricular Arrhythmia In Isolated Perfused Rat Hearts

Objective:The aim of this study was to investigate the effects of substance P(SP) on norepinephrine(NE)-induced ventricular arrhythmia and the underlying mechanism of the anti-arrhythmia of SP.Methods:Healthy male SD rats weighing 250-300 g were used in the experiment.The animals were anesthetized with 25%urethane(1.4-1.8 ml,i.p.).The heart of the animal was excised and perfused in a Langendorff apparatus.The testing agents were administered to the isolated hearts via the perfusion system after 10 min stabilization.ECG was continuously monitored and recorded.Ventricular arrhythmia was counted and analyzed.The study was carried out in 6 groups of animals.(1) Control group:to examine the morbidity of ventricular arrhythmia in isolated perfused rat heart.(2) NE group:to test the changes in the morbidity of ventricular arrhythmia during treatment with NE(10^-5M) in isolated rat heart.(3) NE+SP group:to investigate the effects of SP on NE induced cardiac arrhythmia changes of isolated rat heart was performed.(4) NE+SP+NK-1 receptor antagonist group:to explore the effect neurokinin-1(NK-1) receptor antagonist([D-Arg¹,D-Phe⁵,D-Trp^7,9,Leu¹¹]-Substance P,D-SP) on the action of SP on NE induced cardiac arrhytnmia.(5) D-SP group:to examine effect of D-SP alone(10^-7M,10^-8M,10^-9M) on cardiac arrhythmia of isolated rat heart.(6) D-SP+NE group:to study on the effects of D-SP on NE induced cardiac arrhythmia changes of isolated rat heart.Results:(1) The rate of cardiac ventricular arrhythmia was significantly increased in group NE⁵(NE10^-5M) and D-SP⁷(D-SP10^-7M) as compared with control group.(2) Cardiac ventricular arrhythmia was significantly decreased in group NE⁵SP⁶ (NE10^-5M+SP10^-6M) and NE⁵SP⁷(NE10^-5M+SP10^-7M) as compared with group NE⁵ (NE10^-5M).(3) Cardiac ventricular arrhythmia was significantly increased in group NE⁵SP⁷D-SP⁷ (NE10^-5M+SP10^-7M+D-SP10^-7M),NE⁵SP⁷D-SP⁸(NE10^-5M+SP10^-7M+D-SP10^-8M) and NE⁵SP⁷D-SP⁹(NE10^-5M+SP10^-7M+D-SP10^-9M) as compared with group NE⁵SP⁷ (NE10^-5M+SP10^-7M). Conclusions:NE could induce ventricular arrhythmia on normal isolated rat hearts.SP can attenuate NE-induced ventricular arrhythmia,mediated by NK-1 receptor.Endogenous SP may be involved in the regulation of cardiac activity through modulation of adrenergic mechanisms.