Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury.
The role of a local angiotensin system in the vascular response to arterial injury was investigated by administering the angiotensin-converting enzyme (CE) inhibitor cilazapril to normotensive rats in which the left carotid artery was subjected to endothelial denudation and injury by balloon catheterization. In control animals, by 14 days after balloon injury, the processes of smooth muscle cell (SMC) proliferation, migration of SMCs from the media to the intima, and synthesis of extracellular matrix produced marked thickening of the intima, with reduction of the cross-sectional area of the lumen. However, in animals that received continuous treatment with the CE inhibitor, neointima formation was decreased (by about 80 percent), and lumen integrity was preserved. Thus, the angiotensin-converting enzyme may participate in modulating the proliferative response of the vascular wall after arterial injury, and inhibition of this enzyme may have therapeutic applications to prevent the proliferative lesions that occur after coronary angioplasty and vascular surgery.
Powell
J S
JS
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Clozel
J P
JP
Müller
R K
RK
Kuhn
H
H
Hefti
F
F
Hosang
M
M
Baumgartner
H R
HR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D017315:Cilazapril / Q000031:analogs & derivatives; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; C045980:cilazaprilat