Inhibitor of angiotensin-converting enzyme modifies myointimal origin in an arterial autograft model.
Pharmacologic modulation by an inhibitor of angiotensin-converting enzyme (IACE: cilazapril) of vascular proliferative response to a full-thickness arterial injury (autograft) was studied in rats. An arterial autograft 5 mm long was made in the right common iliac artery of 50 female Sprague-Dawley rats (weight 250-300 g) by microsurgical techniques. The animals were divided into two study groups: group I (controls), 20 animals that underwent arterial autograft but received no other treatment; and group II (cilazapril-treated), 20 rats that underwent arterial autograft and received cilazapril (Roche), 10 mg/day orally (p.o.) in an excipient of 2% arabic gum, for 4 days before operation. Animals were killed on postoperative days 7, 14, 21, 30, and 50, and grafts were studied by light microscopy, scanning and transmission electron microscopy, and morphometry. In the control group, the hyperplasic response had begun by postoperative day 14 and was established by postoperative day 50. In the medial layer, the muscle cells changed in phenotype from contractile to secretory cells. The adventitia had a highly proliferative appearance. In the cilazapril-treated group, fibrin deposits and platelets formed a layer on the internal elastic lamina. This layer appeared to evolve toward an intimal hyperplasia that became quantifiable by postoperative day 21. The medial layer was clearly thinned and showed intense accumulation of lipid microvacuoles, elastic degeneration, and vacuolized cells. Our results suggest that the use of an inhibitor of ACE modified the origin of the intimal hyperplasia in the arterial autograft model. Enhancement of the thrombogenicity of the luminal surface favors myointimal development by thrombus reorganization.
Buján
J
J
Department of Morphological Sciences and Surgery (Surgical Research Laboratory), School of Medicine, University of Alcalá de Henares, Madrid, Spain.
Bellón
J M
JM
Jurado
F
F
Dominguez
B
B
Gimeno
M J
MJ
García-Honduvilla
N
N
Hernando
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000637:transplantation*; D002455:Cell Division / Q000187:drug effects; D017315:Cilazapril / Q000494:pharmacology; D005260:Female; D006965:Hyperplasia / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D008866:Microsurgery; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000637:transplantation*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous
D000806:Angiotensin-Converting Enzyme Inhibitors; D017315:Cilazapril