NDLI: Growth-inhibitory effect of cyclic GMP- and cyclic AMP-dependent vasodilators on rat vascular smooth muscle cells: effect on cell cycle and cyclin expression

Content Provider	PubMed Central
Author	Kronemann, Nicola Nockher, Wolfgang A. Busse, Rudi Schini-kerth, Valérie B.
Copyright Year	1999
Abstract	The possibility that the antiproliferative effect of cyclic GMP- and cyclic AMP-dependent vasodilators involves an impaired progression of vascular smooth muscle cells (VSMC) through the cell cycle and expression of cyclins, which in association with the cyclin-dependent kinases control the transition between the distinct phases of the cell cycle, was examined. FCS (10%) stimulated the transition of quiescent VSMC from the G0/G1 to the S phase (maximum within 18–24 h and then to the G2/M phase (maximum within 22–28 h). Sodium nitroprusside and 8-Br-cyclic GMP, as well as forskolin and 8-Br-cyclic AMP markedly reduced the percentage of cells in the S phase after FCS stimulation. FCS stimulated the low basal protein expression of cyclin D1 (maximum within 8–24 h) and E (maximum within 8–38 h) and of cyclin A (maximum within 14–30 h). The stimulatory effect of FCS on cyclin D1 and A expression was inhibited, but that of cyclin E was only minimally affected by the vasodilators. FCS increased the low basal level of cyclin D1 mRNA after a lag phase of 2 h and that of cyclin A after 12 h. The vasodilators significantly reduced the FCS-stimulated expression of cyclin D1 and A mRNA. These findings indicate that cyclic GMP- and cyclic AMP-dependent vasodilators inhibit the proliferation of VSMC by preventing the progression of the cell cycle from the G0/G1 into the S phase, an effect which can be attributed to the impaired expression of cyclin D1 and A.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0702305
Ending Page	357
Page Count	9
Starting Page	349
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	1
Volume Number	126
Language	English
Publisher Date	1999-01-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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