Milrinone, a phosphodiesterase inhibitor, suppresses intimal thickening after photochemically induced endothelial injury in the mouse femoral artery

Kazunao Kondo, Kazuo Umemura, Mitsuru Miyaji, Mitsuyoshi Nakashima

研究成果: Article査読

30 被引用数 (Scopus)

抄録

The effect of milrinone, a phosphodiesterase (PDE) inhibitor, on intimal thickening after endothelial denudation was investigated. Intimal thickening was induced in the femoral arteries of mice by a photochemical reaction between rose bengal and transluminal green light which caused endothelial injury followed by platelet adhesion, aggregation, and formation of an occlusive thrombus in the irradiated segment of the mouse femoral artery. In this model, intimal thickening occurred following spontaneous thrombolysis. The intima/media ratio at 21 days after irradiation was 0.556 ± 0.104 in the untreated group. Oral administration of milrinone (0.3-3.0 mg/kg) for 3-21 days suppressed intimal thickening by up to 56% in a dose- and time- dependent manner. In an in vivo experiment using bromodeoxyuridine incorporation, milrinone suppressed cell proliferation at 1.0 mg/kg p.o. On the other hand, the minimum doses of milrinone for suppression of ex vivo platelet aggregation induced by collagen (0.8 μg/ml) or ADP (0.5 μM) were 3.0 and 10.0 mg/kg, respectively. These results indicate that milrinone may not suppress intimal thickening by inhibiting platelet function but by preventing vascular smooth muscle cell (VSMC) proliferation, probably through a mechanism mediated via 3', 5'-adenosine cyclic monophosphate (cAMP).

本文言語English
ページ(範囲)133-138
ページ数6
ジャーナルAtherosclerosis
142
1
DOI
出版ステータスPublished - 03-01-1999
外部発表はい

All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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