title: The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.
abstract: Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.
authors.affiliation: Department of Medicine, Brigham Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: V J
authors.initials: VJ
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authors.lastname: Bernstein
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authors.lastname: Celermajer
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authors.lastname: Cohen
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authors.lastname: Dahlöf
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authors.lastname: Deanfield
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authors.lastname: Diez
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authors.lastname: Drexler
authors.forename: R
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authors.lastname: Ferrari
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authors.initials: W
authors.lastname: van Gilst
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authors.initials: L
authors.lastname: Hansson
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authors.lastname: Hornig
authors.forename: A
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authors.lastname: Husain
authors.forename: C
authors.initials: C
authors.lastname: Johnston
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authors.initials: H
authors.lastname: Lazar
authors.forename: E
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authors.lastname: Lonn
authors.forename: T
authors.initials: T
authors.lastname: Lüscher
authors.forename: J
authors.initials: J
authors.lastname: Mancini
authors.forename: A
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authors.lastname: Mimran
authors.forename: C
authors.initials: C
authors.lastname: Pepine
authors.forename: T
authors.initials: T
authors.lastname: Rabelink
authors.forename: W
authors.initials: W
authors.lastname: Remme
authors.forename: L
authors.initials: L
authors.lastname: Ruilope
authors.forename: M
authors.initials: M
authors.lastname: Ruzicka
authors.forename: H
authors.initials: H
authors.lastname: Schunkert
authors.forename: K
authors.initials: K
authors.lastname: Swedberg
authors.forename: T
authors.initials: T
authors.lastname: Unger
authors.forename: D
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authors.lastname: Vaughan
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authors.lastname: Weber
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002319:Cardiovascular System / Q000201:enzymology / Q000503:physiopathology; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000503:physiopathology; D007674:Kidney Diseases / Q000201:enzymology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A