Protective effects of bradykinin on the ischaemic heart: implication of the B1 receptor.
1. We studied the role of bradykinin (BK) and its active metabolite Des-Arg9-BK on noradrenaline release in association with the incidence of ventricular arrhythmias at reperfusion of the ischaemic myocardium. 2. Experiments were performed in Langendorff perfused isolated hearts of rats subjected to 30 min no flow followed by 5 min reperfusion. The electrocardiogram was monitored continuously and noradrenaline was measured in the effluent as well as in the myocardial tissue. 3. In untreated hearts, cumulative noradrenaline overflow following global ischaemia reached 226 +/- 35 pmol g-1 of heart (n = 8, P < 0.05) during the 5 min of reperfusion along with ventricular tachycardia and/or fibrillation. A decrease in myocardial noradrenaline (-31%) was also observed. 4. Bradykinin perfused at concentrations between 0.01 and 1 microM, 10 min before flow was stopped and at reperfusion, inhibited noradrenaline overflow in a concentration-dependent manner. At a concentration of 1 microM, bradykinin completely abolished noradrenaline overflow. For the same concentration of bradykinin, myocardial noradrenaline contents were significantly higher (n = 5-8, P < 0.05). Ventricular fibrillation but not ventricular tachycardia was also prevented. 5. Des-Arg9-BK (0.1 microM) in the same experimental conditions had similar effects. While Hoe 140, a selective antagonist at B2 receptors, did not abolish the effects of bradykinin, Lys [Leu8] Des-Arg9-BK, an antagonist at B1 receptors, abolished the effects of both Des-Arg9-BK and bradykinin. 6. These results suggest that the cardioprotective action of bradykinin in the preparation may be mediated partially by an inhibitory effect on noradrenaline liberation which could be mediated by the activation of B1 receptors.
Centre de recherche, Hôpital du Sacré-Coeur de Montréal, Québec, Canada.
R
R
Chahine
A
A
Adam
N
N
Yamaguchi
R
R
Gaspo
D
D
Regoli
R
R
Nadeau
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin; D009638:Norepinephrine