Paradoxical action of desipramine on the modulatory effect of bradykinin on noradrenaline release in a model of metabolic anoxia in rat isolated atria.
We have previously shown that bradykinin (BK) can modulate the release of noradrenaline (NA) in a model of metabolic anoxia in the rat isolated atria. In this study, we tested the effect of an inhibitor of NA reuptake, desipramine, on the modulatory action of BK on NA release in this experimental model. Atria were isolated from Wistar rats and inserted into a perfusion system. After an equilibration period of 20 min, the perfusate was collected every 5 min for a period of 85 min, during which the atria were field stimulated (5 Hz, 2 ms, 50 mA, 60 s) at 10 (S1) and 75 (S2) min. Desipramine (1 microM) was present throughout the experimental procedures. The metabolic anoxia was started 40 min before S2 by replacing O2 with N2 and by removing glucose. The drugs were added 20 min before S2, and their effects were assessed by the ratio S2/S1. The spontaneous release of NA was not changed by the anoxic procedure, which significantly increased the electrically stimulated induced (S-I) release of NA. BK (30 nM) significantly increased the S-I release of norepinephrine under normoxic conditions. However, following anoxia, both BK and the B1 receptor agonist des-Arg9-BK (100 nM) significantly inhibited the S-I release of NA. The inhibition induced by BK was prevented by selective antagonists for B1 and B2 receptors. These observations contrast with the results obtained without desipramine, where BK, but not des-Arg(9)-BK, inhibited the S-I release of NA during anoxia. Therefore, blockade of NA reuptake during metabolic anoxia appears to alter the modulatory effect of kinins on NA release via the B1 receptor in the rat isolated atria.
Foucart
S
S
Département de physiologie, Faculté de médecine, Université de Montréal, QC, Canada.
Grondin
L
L
Couture
R
R
Nadeau
R
R
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D015687:Cell Hypoxia / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology*; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018341:Receptors, Adrenergic, alpha-2; D018002:Receptors, Bradykinin; D001920:Bradykinin; D003891:Desipramine; D009638:Norepinephrine