Foucart S, Grondin L, Couture R, Nadeau R
Département de physiologie, Faculté de médecine, Université de Montréal, QC, Canada.
Can J Physiol Pharmacol. 1997 Jun;75(6):639-45.
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.
采用代谢性缺氧模型，研究缓激肽（BK）对离体大鼠心房去甲肾上腺素（NA）释放的调节作用。从Wistar大鼠分离出心房并置于灌注系统中。在20分钟的平衡期后，每5分钟收集一次灌注液，持续85分钟，在此期间，心房在第10分钟（S1）和第75分钟（S2）接受场刺激（5Hz，2ms，50mA，60秒）。在S2前40分钟，通过用N2替代O2并去除葡萄糖来启动代谢性缺氧。在S2前20分钟加入药物，并通过S2/S1比值评估其对NA释放的影响。缺氧程序显著增加了NA的自发释放和电刺激诱导（S-I）释放。在常氧条件下，BK（30nM）显著增加了NA的S-I释放。然而，在缺氧条件下，BK对NA的S-I释放没有影响，但抑制了其自发释放。与B2受体拮抗剂HOE-140（100nM）共同给药时，BK在缺氧期间显著增加了NA的S-I释放，而与B1受体拮抗剂Leu3-des-Arg9-BK（100nM）共同给药时，BK显著抑制了该释放。给予去-Arg9-BK（100nM）对缺氧后NA的S-I流出没有影响，尽管其与B1拮抗剂共同给药导致NA的S-I流出显著抑制。目前的结果表明，在40分钟的代谢性缺氧后，BK通过激活B2受体抑制NA释放。因为这种抑制仅在存在B1受体拮抗剂时才能观察到，这可能意味着缺氧所揭示的B1受体激活参与了NA释放的促进作用。
