Molecular and Cellular Biochemistry

, Volume 272, Issue 1–2, pp 19–28 | Cite as

Role of atrial natriuretic peptide in the suppression of lysophosphatydic acid-induced rat aortic smooth muscle (RASM) cell growth

  • P. M. Baldini
  • P. de Vito
  • F. D’aquilio
  • D. Vismara
  • F. Zalfa
  • C. Bagni
  • R. Fiaccavento
  • P. Di Nardo


Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological functions. In the present study we investigated the possible role of atrial natriuretic peptide (ANP), a hormone affecting cardiovascular homeostasis and inducing antimitogenic effects in different cell types, on LPA-induced cell growth and reactive oxygen species (ROS) production in rat aortic smooth muscle (RASM) cells. Both LPA effects on cell growth and levels of ROS were totally abrogated by physiological concentrations of ANP, without modifying the overexpression of LPA-receptors. These effects were also affected by cell pretreatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Moreover, the LPA-induced activation of Akt, a downstream target of PI3K, was completely inhibited by physiological concentrations of ANP, which were also able to inhibit p42/p44 phosphorylation. Taken together, our data suggest that PI3K may represent an important step in the LPA signal transduction pathway responsible for ROS generation and DNA synthesis in RASM cells. At same time, the enzyme could also represent an essential target for the antiproliferative effects of ANP.


atrial natriuretic peptide lysophosphatidic acid phosphatidylinositol 3 kinase reactive oxygen species 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • P. M. Baldini
    • 1
    • 4
  • P. de Vito
    • 1
  • F. D’aquilio
    • 1
  • D. Vismara
    • 1
  • F. Zalfa
    • 1
    • 3
  • C. Bagni
    • 1
    • 3
  • R. Fiaccavento
    • 2
  • P. Di Nardo
    • 2
  1. 1.Department of BiologyUniversity of Rome ‘Tor Vergata’RomeItaly
  2. 2.Department of Internal Medicine, Laboratory of Cellular and Molecular CardiologyUniversity of Rome “Tor Vergata”RomeItaly
  3. 3.Istituto di Neuroscienze Sperimentali. Fondazione Santa LuciaIRCCSRomeItaly
  4. 4.Department of BiologyUniversity of Rome “Tor Vergata”RomeItaly

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