Attenuation of epinephrine-induced dysrhythmias by bradykinin: role of nitric oxide and prostaglandins.
Cardiac dysrhythmias are common during anesthesia and surgery. An important precipitating factor of clinically relevant arrhythmias is the introoperative use of epinephrine. Bradykinin acts as an endogenous cardioprotective substance because it suppresses ventricular dysrhythmias induced by ischemia. In this study, we investigated whether bradykinin has a protective effect, preventing the development of dysrhythmias after epinephrine infusion in rats. Because kinins are potent stimulators of the release of nitric oxide and prostaglandins from the endothelium, we investigated whether the protective effect of bradykinin is mediated by these 2 autacoids. Male Sprague-Dawley rats anesthetized with sodium pentobarbital had catheters placed into a carotid artery and both jugular veins. Arterial blood pressure and lead II of the electrocardiogram (ECG) were continuously monitored and recorded. After a steady state was achieved, 1 mg/kg enalapril, an inhibitor of angiotensin I-converting enzyme/kininase II, was given intravenously to all groups except the one treated with losartan. Bradykinin was infused at the initial rate of 0.5 microg/kg per min. Cardiac arrhythmia was induced with 7.5 microg/kg epinephrine intravenously. Dysrhythmia was assessed by counting the number of premature ventricular contractions (PVCs), runs of ventricular tachycardia (V Tach), and missing beats during the first minute after epinephrine. In untreated, control rats, epinephrine caused 10.8 +/- 2.7 PVCs, 0.8 +/- 0.2 runs of V tach, and 11.6 +/- 7.4 missing beats/min. In rats pretreated with bradykinin, the same dose of epinephrine elicited 1.2 +/- 0.5 PVCs, no runs of V tach, and 0.4 +/- 0.4 missing beats/min. This beneficial effect of bradykinin was partially reversed by N-nitro-L-arginine methyl ester (L-NAME) or indomethacin, and completely by L-NAME plus indomethacin or icatibant, but it was not affected by des-Arg9[Leu8]-bradykinin. We conclude that bradykinin, acting on the B2 receptor, attenuates epinephrine-induced dysrhythmia via a mechanism that involves the release of NO and prostaglandins. Although the mechanism is not clear, NO and prostaglandins may prevent epinephrine-induced dysrhythmia and protect the myocardium via a direct action on cardiac neurons.
Rajani
V
V
Department of Anesthesiology and Pain Management, Cook County Hospital, Chicago, Illinois 60612, USA.
Hussain
Y
Y
Bolla
B S
BS
de Guzman
F Q
FQ
Montiague
R R
RR
Igić
R
R
Rabito
S F
SF
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011453:Prostaglandins; D013777:Tetrazoles; D009569:Nitric Oxide; C065679:icatibant; D019808:Losartan; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D004837:Epinephrine