Calcium channel antagonists in the modern era of coronary thrombolysis: Benefit or detriment?

Foley, James W.; Becker, Richard C.

doi:10.1007/bf00051103

Cited by 1 publication

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References 52 publications

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“…CCB also inhibits Ca 2+ ‐mediated migration, proliferation, matrix production and necrosis in vascular smooth muscle cells [11]. The different responses induced by the agents from the same class of drugs raised questions regarding the beneficial or detrimental effects of calcium antagonists [12,13].…”

Section: Introductionmentioning

confidence: 99%

Deleterious effects of nifedipine on smooth muscle cells implies alterations of intracellular calcium signaling

Raicu¹,

Florea²

2001

Fundamemntal Clinical Pharma

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Nifedipine (NIF), a calcium channel blocker (CCB) from the first generation of dihydropyridines, induces detrimental effects on patients with cardiovascular diseases. We designed experiments to study, at cellular and molecular level, the mechanisms involved in the induction of deleterious effects by this drug. To this purpose, cultured human smooth muscle cells (HSMC) were used. The effect of NIF and two other CCB (FEL, AML) and inhibitors of intracellular signaling pathways (RR, TG, CAF and GEN) on intracellular calcium [Ca(2+)]I was determined by spectrofluorimetry using Fura 2 AM assay. The results showed that: (i) 10 microM NIF induced the increase of [Ca(2+)]I above the basal values (202.77 +/- 23.98 nM vs. 48.68 +/- 6.45 nM), an effect that was prevented by RR (50.45 +/- 13.9 nM) and was not induced by the two other CCB; (ii) NIF had a thapsigargin-like effect, because it induced the same release of intracellular calcium as TG (212.1 +/- 25.62 nM); (iii) The response to NIF was reduced by 40% after the inhibition of IP3 receptor (121.21 +/- 26.01 nM) and by 50% after the inhibition of tyrosine kinase (101.91 +/- 7.76 nM). Together, these data demonstrate that NIF produces a deregulation of intracellular calcium homeostasis. The abnormal increase of [Ca(2+)]I is due to the activation of store operated channels from the plasma membrane responsible for capacitative calcium entry, a process modulated by the activity of tyrosine kinase and the Ca(2+)-ATPase pump from the sarcoplasmic reticulum.

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Section: Introductionmentioning

confidence: 99%