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

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalAtherosclerosis
Volume142
Issue number1
DOIs
Publication statusPublished - 03-01-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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