Antiproliferative effects of verapamil enantiomers on vascular smooth muscle cells

L. L. Simpson, F. Zhang, P. R. Standley, J. L. Ram, M. R. Weir, J. R. Sowers

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

There is considerable interest in the role of Ca2+ in the genesis of atherosclerosis and vascular remodeling. Calcium channel blockers impede atherosclerosis in rodents and have been shown to attenuate vascular smooth muscle cell (VSMC) Ca2+ influx. Accordingly, we studied the roles of Ca2+, S- verapamil (an active calcium channel blocker) and R+ verapamil (an inactive channel blocker) on A7R5 VSMC ionic currents and proliferation. During the period of most rapid growth of control cultures (after the first 2-4 days of culture), low-Ca2+ (0.12 mM) medium significantly inhibited proliferation by 39.3% on day 6 (day 5 of low-Ca2+ medium), and inhibition of proliferation by low Ca2+ continued for up to another 6 days (47.9% inhibition after 11 days in low Ca2+). S- verapamil (5 μM), but not R+ verapamil, reduced Ba2+ current through L-type Ca2+ channels, and neither had effects on Ca2+ channels at lower concentrations. S- and R+ verapamil both inhibited VSMC proliferation significantly within 6 days after seeding, and significant inhibition continued to day 12. At 5 μM, a concentration at which S- reduces Ca2+ currents but R+ does not, significant decreases in proliferation by S- were 33.4% at day 6, 25.3% at day 8, 35.9% at day 10, and 40.5% at day 12; and by R+ were 35.2% at day 6, 27.6% at day 8, 38.4% at day 10, and 36.2% at day 12. In summary, low calcium and both the active and inactive verapamil enantiomers inhibit proliferation. Thus, although Ca2+ appears to be important in the proliferation response, the antiproliferative effect of verapamil on VSMC proliferation is independent of the calcium-channel-blocking effect of the drug.

Original languageEnglish (US)
Pages (from-to)46-53
Number of pages8
JournalJournal of Vascular Medicine and Biology
Volume5
Issue number1-2
StatePublished - Oct 19 1994
Externally publishedYes

Keywords

  • calcium channel
  • patch clamp
  • proliferation
  • vascular smooth muscle
  • verapamil

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Simpson, L. L., Zhang, F., Standley, P. R., Ram, J. L., Weir, M. R., & Sowers, J. R. (1994). Antiproliferative effects of verapamil enantiomers on vascular smooth muscle cells. Journal of Vascular Medicine and Biology, 5(1-2), 46-53.