Angiotensin converting enzyme inhibition unmasks the sympathofacilitatory effect of bradykinin in human right atrium.
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-Arg[Hyp3,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.


CONCLUSIONS
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
L C
LC
Universitätsklinik Freiburg, Innere Medizin IV, Freiburg, Germany.
Berlit
T
T
Schwertfeger
E
E
Beyersdorf
F
F
Schollmeyer
P
P
Bohmann
C
C
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011453:Prostaglandins; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin; D009638:Norepinephrine