Pentoxifylline inhibits angiotensin II-induced proliferation in rat vascular smooth muscle cells

Sang Youb Han, Cy Hyun Kim, Yoon Mee Lee, Dae Hee Kim, Kum Hyun Han, Dae-Ryong Cha

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We tested the ability of the drug pentoxifylline to inhibit the activity of the vasoactive hormone angiotensin II in vascular smooth muscle cells (VSMCs). Cell proliferation, intracellular cAMP, and expression of cell cycle proteins were measured in cells isolated from male Sprague-Dawley rats. Angiotensin II significantly induced proliferation in VSMCs p ( < 0.01). Pentoxifylline significantly blocked this induction in a dose-dependent manner (p < 0.05), and a dose of 0.5 mM was sufficient to completely reverse the effect of angiotensin II. Angiotensin II reduced production of cAMP from 34.62 ± 0.59 pmol/mg protein in untreated cells to 17.49 ± 3.30 pmol/mg protein (p < 0.05). cAMP production was restored to 40.68 ± 0.49 and 41.50 ± 1.78 pmol/mg protein in the presence of 1.0 and 2.0 mM pentoxifylline, respectively. In addition, the same treatments increased cAMP production in untreated cells to 54.82 ± 4.40 and 67.68 ± 4.29 pmol/mg protein, respectively (p < 0.05). Angiotensin II significantly upregulated (p < 0.05) cyclin D1 mRNA 2-fold, but not cyclin E, cyclin A, CDK2, CDK4, or P27. Pretreatment with pentoxifylline prevented this effect. Similarly, the drug blocked the ability of angiotensin II to increase the cyclin D1 protein. Conclusion: Pentoxifylline attenuated angiotensin II-induced proliferation by stimulating cAMP production and partially regulating the cell cycle. However, further studies are required to investigate the effects of the drug on the hypertensive vessel wall.

Original languageEnglish
Pages (from-to)744-749
Number of pages6
JournalBiomedical Research (India)
Volume26
Issue number4
Publication statusPublished - 2015 Jan 1

Keywords

  • Angiotensin II
  • cAMP
  • Cell proliferation
  • Pentoxifylline
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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