Modulation of noradrenaline release by B1 and B2 kinin receptors during metabolic anoxia in the rat isolated atria.
A model of metabolic anoxia was used to investigate the modulatory effect of bradykinin (BK) on the release of noradrenaline (NA) in isolated rat atria. 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. 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 on NA release were assessed by the ratio S2/S1. The spontaneous and electrically stimulated induced (S-I) releases of NA were significantly increased by the anoxic procedure. BK (30 nM) significantly increased the S-I release of NA under normoxic conditions. However, under anoxia, BK had no effect on the S-I release of NA but inhibited its spontaneous release. BK coadministered with HOE-140 (100 nM), a B2 receptor antagonist, significantly increased the S-I release of NA during anoxia, whereas the coadministration of BK with Leu3-des-Arg9-BK (100 nM), a B1 receptor antagonist, significantly inhibited that release. Administration of des-Arg9-BK (100 nM) had no effect on the S-I outflow of NA following anoxia, although its coadministration with a B1 antagonist resulted in a significant inhibition of the S-I outflow of NA. The present results suggest that BK inhibits NA release through the activation of a B2 receptor following a 40-min period of metabolic anoxia. Because this inhibition can be observed only in the presence of a B1 receptor antagonist, this could imply that B1 receptor activation, revealed by the anoxia, is involved in the facilitation of NA release.
Foucart
S
S
Département de physiologie, Faculté de médecine, Université de Montréal, QC, Canada.
Grondin
L
L
Couture
R
R
Nadeau
R
R
D000818:Animals; D016275:Atrial Function; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D015687:Cell Hypoxia / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; 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; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin; D009638:Norepinephrine