Noradrenaline Protects In Vivo Rat Heart Against Infarction and Ventricular Arrhythmias Via Nitric Oxide and Reactive Oxygen Species

• Published in: The Journal of surgical research 2011-07, Vol.169 (1), p.9-15
• Main Authors: Imani, Alireza, Ph.D, Faghihi, Mahdieh, Ph.D, Sadr, Sayyed Shahabeddin, Ph.D, Niaraki, Somayeh Sadeghi, BS.c, Alizadeh, Ali Mohammad, Ph.D
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - therapeutic use; Animals; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; Cardiac dysrhythmias; Cardiology. Vascular system; Cyclic N-Oxides - pharmacology; General aspects; Heart; infarction; ischemia/reperfusion; Ischemic Preconditioning, Myocardial - methods; Male; Medical sciences; Models, Animal; Myocardial Infarction - metabolism; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; nitric oxide; Nitric Oxide - metabolism; Norepinephrine - antagonists & inhibitors; Norepinephrine - therapeutic use; oxygen radicals; Prazosin - pharmacology; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Spin Labels; Surgery; ventricular arrhythmias, preconditioning; α 1-adrenoceptor
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2009.10.025

Background Our previous study showed that pretreatment with noradrenaline via opening of the mitochondrial ATP-sensitive potassium channel protects myocardium against ischemia/reperfusion injuries. We have hypothesized that production of nitric oxide (NO) and generation of reactive oxygen species (ROS) are involved in noradrenaline-induced cardioprotection in rat heart. Methods All anesthetized rats underwent 25min of regional ischemia followed by 120min of reperfusion. Animals were randomized to receive one of the following treatment: saline, noradrenaline (2 μg/kg, i.v.), noradrenaline plus prazosin (an α1 -adrenoceptor blocker, 0.5mg/kg, i.v.), noradrenaline plus L-NAME (a nonspecific NOS inhibitor, 10mg/kg, i.v.), noradrenaline plus tempol (a membrane-permeable radical scavenger, 30mg/kg, i.v.), Prazosin alone, only L-NAME and tempol alone. Results Infarct size (% of risk area) was reduced from 49.6 ± 2.4 in saline-control group to 18.2 ± 1.5 in noradrenaline preconditioned group. Administration of prazosin, L-NAME, or tempol prior to noradrenaline injection abolished the observed cardioprotection of noradrenaline (45.5 ± 3, 41.7 ± 4.5 and 38.7 ± 5.4, respectively) and restored infarct size to saline-control rats' level. Incidences and severity of ventricular arrhythmia during ischemia and early reperfusion significantly decreased in noradrenaline preconditioned group compared with saline-control group. This cardioprotective effect of noradrenaline against ventricular arrhythmia was abrogated by administration of prazosin, L-NAME, or tempol. Conclusion Cardioprotection effect of the α1 -adrenoceptor stimulation by noradrenaline was inhibited by L-NAME or tempol in anesthetized rat heart.