title: Esmolol activates endogenous neurokinin activity inhibiting infarction-induced arrhythmias in rats: novel mechanisms of anti-arrhythmia.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Shanxi Medical University and Second Hospital of Shanxi Medical University, 56 South Xinjian Nan Road, Taiyuan 030001, Shanxi, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Han
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D054059:Coronary Occlusion / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D064729:Neurokinin-1 Receptor Antagonists; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018040:Receptors, Neurokinin-1; D013373:Substance P; C045800:substance P, Phe(5)-Trp(7,9)-Leu(11)-; C036604:esmolol; D009638:Norepinephrine
keywords: Acute myocardial infarction; D-SP; Esmolol; NE; NK1-R; Neurokinin; Neurokinin-1 receptor; SP; Ventricular arrhythmias; [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P; neurokinin 1 receptor; norepinephrine; substance P; β1-AR; β1-Adrenergic mechanism; β1-adrenergic receptor