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: Li-Li Wang, Yi Han, Zheng Guo, Shi-Qi Han, Tao Liu
• Journal: Regulatory peptides (Regul Pept) Vol. 186 Pg. 116-22 (Sep 10 2013) ISSN: 1873-1686 [Electronic] Netherlands
• PMID: 23994276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Adrenergic beta-1 Receptor Antagonists
• Anti-Arrhythmia Agents
• Neurokinin-1 Receptor Antagonists
• Propanolamines
• Receptors, Adrenergic, beta-1
• Receptors, Neurokinin-1
• Substance P
• substance P, Phe(5)-Trp(7,9)-Leu(11)-
• esmolol
• Norepinephrine

Topics

• Adrenergic beta-1 Receptor Antagonists (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Arrhythmias, Cardiac (etiology, metabolism, prevention & control)
• Coronary Occlusion (complications, drug therapy, metabolism)
• Drug Evaluation, Preclinical
• Gene Expression
• Male
• Myocardial Infarction (complications, drug therapy, metabolism)
• Myocardium (metabolism, pathology)
• Neurokinin-1 Receptor Antagonists (pharmacology)
• Norepinephrine (metabolism)
• Propanolamines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, beta-1 (metabolism)
• Receptors, Neurokinin-1 (genetics, metabolism)
• Substance P (analogs & derivatives, pharmacology, physiology)