Benazepril on tissue angiotensin-converting enzyme and cellular proliferation in restenosis after experimental angioplasty.
We investigated the role of vascular angiotensin-converting enzyme (ACE) activity, cell proliferation, and the effect of different doses of benazepril on intimal hyperplasia after angioplasty in rabbits. Angioplasty was performed in all left iliac arteries in 28 rabbits. Benazepril was administrated to treatment groups in low (1 mg/kg/day) and high (10 mg/kg/day) doses. Two weeks after angioplasty, vascular ACE activity of the angioplasty subgroup was significantly higher than that of the nonangioplasty subgroup (from 0.44 to 1.19 nmol His-Leu/mg/min; p < 0.01). Strong correlation was demonstrated between vascular ACE activity and intimal area (r = 0.708; p < 0.01). Suppression of vascular ACE activity (59% decrease) and inhibition of intimal hyperplasia (43% decrease) was observed in the high-dose subgroup compared with the angioplasty subgroup without drug intervention (p < 0.01). But in the low-dose subgroup, the level of vascular ACE activity decreased moderately (24.4%; p < 0.05), and the intimal area did not alter significantly. Both the low and high dosage of benazepril resulted in a significant decrease in blood pressure (31 and 44 mm Hg, respectively). Striking correlation was displayed between proliferating-cell nuclear antigen (PCNA)-positive cell percentage and intimal area (r = 0.716; p < 0.01). These results indicated that with excessive expression of vascular ACE, intimal cellular proliferation may play a potential role in restenosis after angioplasty. Benazepril could inhibit intimal hyperplasia by suppressing vascular-tissue ACE.
Li
J
J
Division of Cardiology, Shanghai Sixth People's Hospital, Shanghai Second Medical University, China.
Wanchun
C
C
D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D007703:Peptidyl-Dipeptidase A; C044946:benazepril