Inhibitory effect of perindopril, a novel angiotensin-converting enzyme inhibitor, on neointima formation after balloon injury in rats and cholesterol-fed rabbits.
We investigated the effect of perindopril, a novel angiotensin-converting enzyme (ACE) inhibitor, on neointima formation in vessel walls after balloon injury in rats (carotid artery) and cholesterol-fed rabbits (thoracic aorta). Continuous treatment with perindopril significantly reduced neointima formation in both species, as compared with the control group: intima/media (I/M) ratio (rats -62%; p < 0.001; rabbits -25%, p < 0.05); neointima area (rats -65%, p < 0.01; rabbits -24%, p < 0.05). These changes involved reduction of intimal smooth muscle cells (SMC) in rats and of macrophages in rabbits. Furthermore, perindopril also significantly decreased ACE activity in both aortic tissue and serum [11.38 +/- 0.87 vs. 34.93 +/- 6.44 pmol His-Leu (HL)/mg/min (p < 0.01) and 2.79 +/- 0.28 vs. 38.50 +/- 5.41 pmol HL/mg/min (p < 0.001), respectively], aortic contraction evoked by angiotensin I (AI) and mean blood pressure (BP, 84.9 +/- 3.5 vs. 109.3 +/- 3.8 mm Hg, p < 0.001) as compared with control values. These results indicate that perindopril may reduce neointima formation by suppressing the aortic renin-angiotensin system (RAS). These findings indicate that perindopril may be capable of preventing restenotic lesions after angioplasty in humans [corrected].
Shibutani
T
T
Exploratory Research Laboratories II, Daiichi Pharmaceutical, Tokyo, Japan.
Kanda
A
A
Ishigai
Y
Y
Mori
T
T
Chiba
K
K
Tanaka
M
M
Tachizawa
H
H
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D020212:Carotid Artery Injuries; D002455:Cell Division / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000293:injuries; D007211:Indoles / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D020913:Perindopril; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002791:Cholesterol, Dietary; D007211:Indoles; D020913:Perindopril