MODULATION OF NORADRENALINE RELEASE BY B-1 AND B-2 KININ RECEPTORS DURING METABOLIC ANOXIA IN THE RAT ISOLATED ATRIA

A model of metabolic anoxia was used to investigate the modulatory eff ect of bradykinin (BK) on the release of noradrenaline (NA) in isolate d rat atria. Atria were isolated from Wistar rats and inserted into a perfusion system. After an equilibration period of 20 min, the perfusa te 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 (S-1) and 75 (S-2) min. The metabolic anoxia was started 40 min before S-2 by re placing O-2 with N-2 and by removing glucose. The drugs were added 20 min before S-2, and their effects on NA release were assessed by the r atio S-2/S-1. 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 normox ic conditions. However, under anoxia, BK had no effect on the S-I rele ase of NA but inhibited its spontaneous release. BK coadministered wit h HOE-140 (100 nM), a B-2 receptor antagonist, significantly increased the S-I release of NA during anoxia, whereas the coadministration of BK with Leu(8)-des-Arg(9)-BK (100 nM), a B-1 receptor antagonist, sign ificantly inhibited that release. Administration of des-Arg(9)-BK (100 nM) had no effect on the S-I outflow of NA following anoxia, although its coadministration with a B-1 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 B-2 receptor follow ing a 40-min period of metabolic anoxia. Because this inhibition can b e observed only in the presence of a B-1 receptor antagonist, this cou ld imply that B-1 receptor activation, revealed by the anoxia, is invo lved in the facilitation of NA release.