ACE inhibitors are endothelium dependent vasodilators of coronary arteries during submaximal stimulation with bradykinin.
OBJECTIVE
The effect of angiotensin converting enzyme (ACE) inhibitors on vascular tone of isolated coronary arteries was determined in the presence of bradykinin and other vasodilators to elucidate the mechanisms leading to augmented bradykinin effects during ACE inhibition.


METHODS
Rings of isolated bovine and human coronary arteries were mounted in organ chambers for measurement of isometric force. The effects of lisinopril, enalaprilat, and captopril were investigated in the presence of submaximal concentrations of bradykinin or other vasodilators.


RESULTS
ACE inhibitors alone did not affect vascular tone. Threshold concentrations of bradykinin (10(-10) M), kallidin (10(-9.5) M), and the slowly degraded bradykinin agonists D-Arg(Hyp3)-bradykinin (10(-9.5) M) and [Hyp3-Tyr(Me)8]-bradykinin (10(-10.5) M) caused partial relaxation of bovine rings with endothelium. Subsequent addition of ACE inhibitors markedly potentiated the relaxations to the kinins. Bradykinin concentrations in the organ bath measured by a specific bradykinin radioimmunoassay remained stable during the addition of lisinopril. Variation of the exposure time to bradykinin (10 to 60 min) did not affect the relaxations to the ACE inhibitor. The relaxations to lisinopril were not observed after either removal of the endothelium or incubation with nitro-l-arginine or the bradykinin-2 receptor antagonist Hoe 140. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium dependent relaxation to lisinopril and captopril was also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M), but not in those treated with substance P (10(-8) M).


CONCLUSIONS
ACE inhibitors selectively potentiate endothelium dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries by a local mechanism. This effect on endothelial cells might occur in addition to augmented bradykinin concentrations in the blood and reduced angiotensin II generation.
German Heart Institute Berlin, Department of Internal Medicine and Cardiology.
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W
Auch-Schwelk
C
C
Bossaller
M
M
Claus
K
K
Graf
M
M
Gräfe
E
E
Fleck
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D017706:Lisinopril; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D017706:Lisinopril; D001920:Bradykinin