Bradykinin significantly enhanced the release of noradrenaline in human atrium only when its enzymatic degradation was prevented by the ACE inhibitor captopril.
ACE inhibition unmasks a sympathofacilitatory effect of bradykinin in human atrial tissue, likely via B2-receptor activation and prostaglandin release.
OBJECTIVE: To investigate the role of angiotensin converting enzyme (ACE) inhibition in bradykinin-mediated modulation of noradrenaline release in human and rat atrium. METHODS: Human and rat atrial slices were incubated with 3H-noradrenaline, superfused with Krebs-Henseleit solution and stimulated electrically at 5 Hz. The stimulation-induced outflow of radioactivity was taken as an index of endogenous noradrenaline release. RESULTS: In the absence of ACE inhibition 0.01-1 micromol/l bradykinin failed to alter the release of noradrenaline in human atrium. In contrast, 0.001-0.1 micromol/l bradykinin enhanced the release of noradrenaline in rat atrium. In the presence of 3 micromol/l of the ACE inhibitor captopril, however, bradykinin significantly enhanced the release of noradrenaline in human atrium. The bradykinin B1-receptor agonist (Des-Arg9)-bradykinin (0.01-1 micromol/l) had no effect on the release of noradrenaline in human atrium both in the absence and in the presence of 3 micromol/l captopril. Captopril (3 micromol/l) potentiated the facilitatory effect of bradykinin in rat atrium. The selective bradykinin B2-receptor antagonist D-ArgHyp3,Thi5, D-Tic7,Oic8-bradykinin (Hoe 140, 0.3 micromol/l) and the cyclo-oxygenase inhibitor indomethacin (10 micromol/l) reduced the facilitatory effect of bradykinin significantly in the presence of captopril in rat and human atrium. Prostaglandin F2alpha (0.1 micromol/l), prostaglandin E2 (0.3 micromol/l) and the thromboxane A2 receptor agonist U-46 619 (0.1 micromol/l) enhanced the release of noradrenaline in human atria, whereas 0.1 micromol/l prostaglandin I2 had no effect. CONCLUSION: These data suggest that bradykinin facilitates the release of noradrenaline in human and rat atrium by activation of bradykinin receptors of the B2-subtype and subsequent release of facilitatory prostaglandins. The facilitatory effect of bradykinin in human atrium can only be demonstrated when its enzymatic degradation is prevented by ACE inhibition.
Rump et al. (Sat,) reported a other. Bradykinin with ACE inhibitor (captopril) vs. Bradykinin without ACE inhibition was evaluated on Stimulation-induced outflow of radioactivity (index of endogenous noradrenaline release). Bradykinin significantly enhanced the release of noradrenaline in human atrium only when its enzymatic degradation was prevented by the ACE inhibitor captopril.