Endogenous neurokinin and
adrenergic mechanisms might co-participate in the pathology of acute
myocardial infarction (MI). This study sought to investigate the role of endogenous neurokinin and its relationship with β1-adrenergic mechanism in the
infarction induced arrhythmias. In 60min of MI in rats, the contents of
substance P (SP), a native agonist of
neurokinin 1 receptor (NK1-R),
norepinephrine (NE), NK1-R and β1-adrenergic receptor in the myocardium at risk of
ischemia were examined and the ventricular arrhythmias were analyzed. The effects of pretreatment with D-SP (152ng/kg), a specific antagonist of NK1-R,
esmolol (10mg/kg), a specific blocker of β1-adrenergic receptor, and a combination of the two blockers were studied. The results showed that the overlaps of up-regulation of NE, SP and the increase of ventricular arrhythmias were observed. D-SP exacerbated the episodes and duration of VT & VF by 54% and 104%, respectively (all P<0.05).
Esmolol inhibited the morbidity rate, the episodes and the duration of VT & VF by 66%, 92% and 95%, respectively. Surprisingly,
esmolol significantly attenuated the arrhythmogenic effect of D-SP throughout the MI, beyond the time span of
esmolol action, during which a significant up-regulation of the NK1-R (by 19%, P<0.05) was detected. In conclusion, the findings of this study may indicate an
anti-arrhythmic effect of endogenous neurokinin mechanism, through the activation of which, via up-regulation of NK1 receptor,
esmolol may exert its
anti-arrhythmic action at the early time of acute
myocardial infarction.