Effects of Magnesium Lithospermate B and its Analogues on Ca2+ Homeostasis in Cultured Rat Thoracic Aorta Vascular Smooth Muscle Cells

Magnesium lithospermate B (MLB), sodium rosmarinate (SR), and magnesium lithospermate (ML) are biologically active components isolated from aqueous extracts of the Chinese medicine Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge (Labiatae). These compounds share similar chemical structures of polyphenols and oligomer condensates with caffeic acid. In this study, we compared the effects of MLB, ML, and SR on intracellular Ca2+ concentrations ([Ca2+](i)) in cultured rat thoracic aorta vascular smooth muscle cells (VSMCs), using the Ca2+-sensitive dye, Fluo-3, as an indicator. In our experiments, MLB, ML, and SR did not affect the basal value of [Ca2+](i) in VSMCs. In the absence of extracellular Ca2+, the [Ca2+](i) increase in VSMCs induced by 20 mu M ATP was attenuated by MLB, ML, and SR in a dose-dependent manner. Moreover, under this condition, MLB suppressed the increase in [Ca2+](i) in VSMCs induced by 1 mu M thapsigargin, but not ML or SR. In the presence of extracellular Ca2+, the [Ca2+](i) increase in VSMCs induced by 60 mM KCl was attenuated by MLB and SR in a close-dependent manner, but not by ML. These results suggest that MLB, ML and SR regulate Ca2+ homeostasis in VSMCs via different pathways. Our findings should aid in elucidating the mechanisms of the vasodilator action of aqueous extracts of Salvia miltiorrhiza.