The endothelium controls the tone of the underlying vascular smooth muscle
mainly through the production of vasodilator mediators. In some cases. this
function is hampered by the release of constrictor substances. The endothe
lial mediators are also involved in the regulation by the endothelium of va
scular architecture and the blood cell-vascular wall interactions. The endo
thelium-derived factors comprise nitric oxide (NO), prostacyclin, and a sti
ll unknown endothelium-derived hyperpolarizing factor(s) (EDHF). In most va
scular diseases, the vasodilator function of the endothelium is attenuated.
In advanced atherosclerotic lesions, endothelium-dependent vasodilatation
may even be abolished. Various degrees and forms of endothelial dysfunction
exist, including (1) the impairment of G(alpha i) proteins, (2) less relea
se of NO, prostacyclin and/or EDHF, ( 3) increased release of endoperoxides
. (4) increased production of reactive oxygen species, (5) increased genera
tion of endothelin-l, and (6) decreased sensitivity of the vascular smooth
muscle to NO, prostacyclin and/or EDHF. The levels of bradykinin and angiot
ensin II within the vascular wall are controlled by angiotensin-converting
enzyme (ACE). ACE degrades bradykinin and generates angiotensin II. Bradyki
nin stimulates endothelial cells to release vasodilators. The actions of th
e kinin are maintained despite endothelial dysfunction, except in very seve
re arterial lesions. Angiotensin II may be in part responsible for endothel
ial dysfunction because it induces resistance to the vasodilator action of
NO. Thus, impairment of the generation of angiotensin II blocks the direct
and indirect vasoconstrictor effect of the peptide. By potentiating bradyki
nin. ACE inhibitors promote the release of relaxing vasodilator mediators t
o restore vasodilator Function, and to prevent platelet aggregation as well
as the recruitment of leukocytes to the vascular wall. (C) 1999 Academic P
ress.