The potential antiarrhythmic effects of exogenous and endogenous bradykinin in the ischaemic rat heart in vivo.
BACKGROUND
Recent studies have shown that bradykinin decreases the incidence of ischaemic arrhythmias in dogs and may also mediate the antiarrhythmic effects of preconditioning in this species. We investigated the effects of exogenously administered bradykinin on the severity of ischemic arrhythmias and the role of endogenously released bradykinin, acting on B2-receptors, in preconditioning in anaesthetized rats.


METHODS
In protocol 1, male rats were subjected to a single 30 min occlusion of the left main coronary artery and received left ventricular infusions of bradykinin (30 ng to 10 micrograms/kg/min) or saline. In protocol 2, rats were pretreated with the B2-receptor antagonist HOE 140 (40 and 400 micrograms/kg intravenous bolus) 10 min before coronary artery occlusion. In protocol 3, rats were preconditioned by a 3 min coronary occlusion followed by 10 min of reperfusion before a sustained 30 min occlusion. Saline or HOE 140 was given 10 min before the preconditioning protocol. In all groups, the number and severity of ventricular arrhythmias were determined during the 30 min coronary occlusion.


RESULTS
In protocol 1, none of the doses of bradykinin had any significant effect on the total number of ventricular ectopic beats (1512 +/- 252 in saline-treated controls versus 1337 +/- 302 with the highest dose of bradykinin tested) or on the incidence of ventricular tachycardia or ventricular fibrillation. The two higher doses of bradykinin (1 and 10 micrograms kg/min) caused a reduction in blood pressure soon after infusion began, although this was not maintained for the duration of the experiment. In protocol 2, HOE 140, in doses that produced a sustained antagonism to the depressor response to bradykinin, had no effect on either arrhythmia count or the incidence of ventricular fibrillation in rats subjected to a single 30 min coronary occlusion. In protocol 3, a 3 min preconditioning occlusion in saline-treated rats reduced arrhythmia counts from 1046 +/- 196 in non-preconditioned rats to 76 +/- 44 in preconditioned rats, and reduced the incidences of ventricular tachycardia and ventricular fibrillation from 100 to 50% and from 75 to 7%, respectively. Neither dose of HOE 140 tested reversed these antiarrhythmic effects of preconditioning.


CONCLUSIONS
These results suggest that bradykinin is not protective against ischaemic arrhythmias in rats in vivo, whether given exogenously or released endogenously. Furthermore, in contrast to other species, bradykinin does not appear to play a role in the antiarrhythmic effect of ischaemic preconditioning.
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK.
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Wainwright
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control
D000319:Adrenergic beta-Antagonists; C065679:icatibant; D001920:Bradykinin