Noradrenaline protects in vivo rat heart against infarction and ventricular arrhythmias via nitric oxide and reactive oxygen species.
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 25 min of regional ischemia followed by 120 min of reperfusion. Animals were randomized to receive one of the following treatment: saline, noradrenaline (2 μg/kg, i.v.), noradrenaline plus prazosin (an α(1)-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, 30 mg/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.


CONCLUSIONS
Cardioprotection effect of the α(1)-adrenoceptor stimulation by noradrenaline was inhibited by L-NAME or tempol in anesthetized rat heart.
Imani
Alireza
A
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran.
Faghihi
Mahdieh
M
Sadr
Sayyed Shahabeddin
SS
Niaraki
Somayeh Sadeghi
SS
Alizadeh
Ali Mohammad
AM
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000517:prevention & control*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels
D000316:Adrenergic alpha-Agonists; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D009569:Nitric Oxide; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D011224:Prazosin