Kinin-induced prolongation of action-potential duration in right ventricular muscle from rat: involvement of B1 and B2 receptors.
Previous work has shown that, in rat ventricular muscle, bradykinin (BK) causes a dose-dependent increase in action potential duration (APD), an action that may be responsible for APD prolongation by captopril (kininase II). To determine which kinin receptor might be involved in APD prolongation, we studied the effects of B1- and B2-receptor agonists, as well as those of antagonists and mergepta (a kininase I inhibitor) added during BK superfusion. Action potentials were recorded by using the standard glass microelectrode technique in rat ventricular muscle preparations. Action-potential characteristics were compared between preparations superfused with peptide/drug-free Tyrode's solution (control group) and preparations superfused with peptide/drug-containing solution. APD was significantly longer in preparations superfused with BK (10(-8) M) than in the control group. The APD prolongation induced by BK, a known B2-receptor agonist, was significantly reduced by Hoe 140 (a B2 antagonist) and also by Lys[Leu8]des-Arg9-BK (a B1 antagonist), an action presumably related to inhibition of B1 receptor stimulation by the BK metabolite des-Arg9-BK. When mergepta was added in the presence of BK, APD prolongation by BK was significantly reduced, an effect that could have been related to reduced B1-receptor stimulation after inhibition of the endogenous generation of des-Arg9-BK by kininase I. Sar4-[d-Phe8]des-Arg9-BK, a B1-receptor agonist that is not degraded by kininase II, also prolonged APD. We conclude that both B1 and B2 receptors may be involved in APD prolongation induced in rat ventricular muscle preparations.
Gouin
L
L
Faculté de médecine, Département de pharmacologie, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Québec, Canada.
Cardinal
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R
Adam
A
A
Drapeau
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G
Nadeau
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R
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology; D004594:Electrophysiology; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*; D016278:Ventricular Function, Right / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D011480:Protease Inhibitors; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; C065679:icatibant; D002216:Captopril; D015097:3-Mercaptopropionic Acid; D001920:Bradykinin