Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans.
BACKGROUND
The angiotensin-converting enzyme (ACE) not only generates angiotensin II but is also the main enzyme that destroys bradykinin. It has been hypothesized, therefore, that bradykinin is involved in the vascular effects of ACE inhibitors. However, its contribution has never been demonstrated in humans because of the lack of specific bradykinin receptor antagonists.


RESULTS
High-resolution ultrasound and Doppler were used to measure radial artery diameter and blood flow in 10 healthy volunteers. The vascular effects of the ACE inhibitor quinaprilat, the selective bradykinin B2-receptor antagonist icatibant, and their combination were determined at rest, during reactive hyperemia (with increased flow causing endothelium-mediated, flow-dependent dilation), and during sodium nitroprusside, causing endothelium-independent dilation. Neither icatibant nor quinaprilat affected arterial diameter or blood flow at rest. However, icatibant reduced flow-dependent dilation by 33%, and quinaprilat increased flow-dependent dilation over baseline by 46%. After coinfusion of quinaprilat and icatibant, flow-dependent dilation was reduced to a similar extent as after infusion of icatibant alone.


CONCLUSIONS
ACE inhibition enhances flow-dependent, endothelium-mediated dilation in humans by a bradykinin-dependent mechanism. This observation indicates that accumulation of endogenous bradykinin is involved in the vascular effects of ACE inhibitors in humans.
Hornig
B
B
Abteilung Kardiologie, Medizinische Hochschule Hannover, Germany.
Kohler
C
C
Drexler
H
H
D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D006940:Hyperemia; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D017534:Radial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects*; D044005:Tetrahydroisoquinolines; D018608:Ultrasonography, Doppler; D014664:Vasodilation
D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D009599:Nitroprusside; C054501:quinaprilat; C065679:icatibant; D001920:Bradykinin