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Growth-inhibitory effect of cyclic GMP- and cyclic AMP-dependent vasodilators on rat vascular smooth muscle cells:

N Kronemann1, W A Nockher, R Busse

  • 1Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.

British Journal of Pharmacology
|March 2, 1999
PubMed

Insights

Cyclic GMP- and cyclic AMP-dependent vasodilators inhibit vascular smooth muscle cell proliferation by blocking cell cycle progression. This effect is linked to reduced expression of key cell cycle proteins, cyclin D1 and cyclin A.

Area of Science:

  • Vascular Biology
  • Cell Cycle Regulation
  • Pharmacology

Background:

  • Vascular smooth muscle cell (VSMC) proliferation is crucial for vascular health.
  • Cyclic nucleotides (cGMP and cAMP) are known regulators of VSMC function.
  • The precise mechanisms by which vasodilators influence VSMC cell cycle progression are not fully understood.

Purpose of the Study:

  • To investigate the antiproliferative effects of cGMP- and cAMP-dependent vasodilators on VSMCs.
  • To determine if these vasodilators impair VSMC cell cycle progression and cyclin expression.
  • To elucidate the role of cyclins D1, E, and A in mediating these effects.

Main Methods:

  • VSMCs were stimulated with fetal calf serum (FCS) to induce cell cycle progression.
  • Cells were treated with vasodilators (sodium nitroprusside, 8-Br-cGMP, forskolin, 8-Br-cAMP).
  • Cell cycle phase distribution, cyclin protein, and mRNA expression were analyzed using flow cytometry and molecular techniques.

Main Results:

  • FCS stimulated VSMC transition from G0/G1 to S and G2/M phases.
  • Vasodilators significantly reduced the percentage of cells in the S phase.
  • FCS-induced expression of cyclin D1 and A proteins and mRNA was inhibited by vasodilators, while cyclin E was minimally affected.

Conclusions:

  • cGMP- and cAMP-dependent vasodilators inhibit VSMC proliferation.
  • This inhibition occurs by preventing cell cycle progression from G0/G1 to S phase.
  • Impaired expression of cyclin D1 and A mediates the antiproliferative effect of these vasodilators.

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