Statins rise cytoplasmic calcium level [Ca2+]i in cultured endothelial cells.

Recently, we have shown that some HMG-CoA reductase inhibitors (statins) induce immediate pleiotropic effects in vascular endothelium both in vivo and in vitro, to mention only PGI 2 -mediated thrombolysis in rats and NO-mediated endothelium-dependent vasodilation in guinea pig coronary circulation. Here we look whether immediate endothelial effect of statins is associated with mobilization of intracellular calcium ions [Ca 2 + ] i in cultured bovine aortic endothelial cells (BAEC). We analyzed the effects of various statins (atorvastatin, cerivastatin, simvastatin, lovastatin and pravastatin at concentration of 10-30 μM) on [Ca 2 + ] i in BAEC in comparison to responses induced by bradykinin (Bk) (10 nM), adenosine diphosphate (1 μM), acetylcholine (100 nM), adrenaline (10 μM), serotonin (10 pM) or calcium ionophore A 23187 (0.1 μM) using FURA-2 according to fluorimetric method of Grynkiewicz et al. Basal [Ca 2 + ] i level in BAEC was between 60 and 100 nM. Bk was the most potent to induce [Ca 2 + ] i response. Δ[Ca 2 + ] i induced by Bk was 331.9 ′ 19.49 nM (n = 36). Δ[Ca 2 + ] i induced by statins (30 μM), i.e. atorvastatin, cerivastatin, simvastatin, lovastatin and pravastatin were 66.4 ′ 7.38% (n = 6), 54.8 ′ 10.12% (n = 5), 58.8 ′ 13.9% (n = 8), 27.7 ′ 7.19% (n = 5) and 0% (n = 5) of the response induced by Bk (10 nM), respectively. In summary, all statins tested, except pravastatin, induce immediate increase in [Ca 2 + ] i in endothelium. This pleiotropic activity of statins in endothelium, most likely not related to the inhibition of HMG-CoA reductase, may represent an intracellular correlate for the immediate release of NO and PGI 2 by these drugs that was reported by us previously.