ACE inhibition, endothelial function and coronary artery lesions. Role of kinins and nitric oxide.
In healthy coronary arteries, the endothelium plays an important role in the regulation of vascular smooth muscle growth and contractility. Furthermore, the endothelium inhibits overt platelet aggregation and prevents the adhesion of white blood cells to, and their infiltration into, the vascular wall. Among the mediators of these functions of endothelial cells, nitric oxide (NO) plays a central role. Moreover, the presence of local kinin-generating enzymatic systems associated with endothelial cells, vascular smooth muscle, platelets, neutrophils and monocytes suggests that bradykinin stimulates endothelial cells to release NO locally. The activation of endothelial cells by bradykinin is inhibited by kininase II, best known as angiotensin converting enzyme (ACE). Hence, ACE inhibitors, in addition to reducing the levels of angiotensin II (a potent stimulus to vascular smooth muscle growth and contraction), cause an amplification of the release of NO and other endothelial mediators that is induced by bradykinin. Independent risk factors for coronary artery disease such as hypertension, diabetes and hypercholesterolaemia reduce the NO-dependent regulation of vascular smooth muscle contractility and growth in otherwise normal coronary arteries. This endothelial dysfunction probably also affects the inhibitory role of NO with regard to platelet aggregation and monocyte infiltration into the vascular wall. In atherosclerotic vessels, the role of NO is severely reduced. In animal models, as well as in patients with coronary artery disease, endothelial dysfunction is improved by treatment with ACE inhibitors. Although in humans the mechanism of the restoration of endothelial function is not known, in animals endogenous kinins and NO are involved. However, it is clear that this process is multifactorial, and thus probably involves both the prevention of the deleterious actions of angiotensin II and the potentiation of bradykinin.
Mombouli
J V
JV
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006706:Homeostasis; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D007704:Kininogens / Q000097:blood; D007705:Kinins / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007704:Kininogens; D007705:Kinins; D009569:Nitric Oxide; D007610:Kallikreins; D012697:Serine Endopeptidases; D001920:Bradykinin