Endothelium-dependent effects of converting-enzyme inhibitors.
Angiotensin-converting enzyme (ACE) inhibitors were designed to prevent the vasoconstrictor influence of the activated renin-angiotensin system. However, it has long been suspected that the vasodilator actions of these compounds are not entirely related to inhibition of the generation of angiotensin II. Bradykinin, which is rapidly degraded by ACE, stimulates the release of endothelium-derived vasodilator mediators, including nitric oxide, endothelium-derived hyperpolarizing factor, and prostacyclin. These mediators do not contribute to the vasodilator effect of bradykinin in every arterial bed. However, the prevention by ACE inhibitors of the degradation of bradykinin-induces an augmentation of the production of these substances and thus potentiates the dilatation evoked by the peptide. The existence of a local kallikrein-kinin system in the vascular wall has been demonstrated, and locally generated kinins contribute to the acute vasodilator actions of ACE inhibitors. ACE inhibitors can potentiate endothelium-dependent dilatations evoked by neurohumoral mediators that are not substrates for ACE. Thus, the vasodilator properties of ACE inhibitors not only reflect inhibition of the renin-angiotensin system but also depend on the enhanced production of endothelium-derived mediators.
Vanhoutte
P M
PM
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.
Boulanger
C M
CM
Illiano
S C
SC
Nagao
T
T
Vidal
M
M
Mombouli
J V
JV
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy; D007610:Kallikreins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D007610:Kallikreins; D001920:Bradykinin