Suppression of arterial intimal hyperplasia by cilostamide, a cyclic nucleotide phosphodiesterase 3 inhibitor, in a rat balloon double‐injury model

• Published in: British journal of pharmacology 2000-05, Vol.130 (2), p.231-241
• Main Authors: Inoue, Yoshihiro, Toga, Kazuyuki, Sudo, Toshiki, Tachibana, Kazue, Tochizawa, Shirou, Kimura, Yukio, Yoshida, Yoji, Hidaka, Hiroyoshi
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Animals; Catheterization; Cell Count - drug effects; cell proliferation; Cells, Cultured; cilostamide; cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 3; Disease Models, Animal; double‐injury model; Hyperplasia - drug therapy; Hyperplasia - pathology; intimal hyperplasia; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - pathology; Phosphodiesterase; Phosphodiesterase Inhibitors - therapeutic use; Proliferating Cell Nuclear Antigen - biosynthesis; Quinolones - therapeutic use; Rats; Rats, Sprague-Dawley; Time Factors; Tunica Intima - drug effects; Tunica Intima - injuries; Tunica Intima - pathology; vascular smooth muscle cells
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703287

The effects of cilostamide, a cyclic nucleotide phosphodiesterase 3 (PDE3) selective inhibitor, on vascular intimal hyperplasia were evaluated using a single‐balloon injury model and a double‐injury model in which the rat common carotid artery was subjected to a second injury at a site injured 14 days previously. In the double‐injury model, the second balloon injury caused more severe intimal hyperplasia (intima/media (IM) ratio, 1.88±0.10) than in the single‐injury model (1.09±0.08). Histopathological study revealed that vascular smooth muscle cells (VSMC) were the predominant cell‐type in the affected neointimal area. Oral administration of cilostamide for 2 weeks after the second injury suppressed intimal hyperplasia in the double‐injury model (30 mg kg−1 bid, 83% inhibition in terms of the IM ratio, P