Fig. 7.

Oatp-mediated statin accumulation is increased in cerebral cortex, but not in hippocampus or cerebellum, after BMP-9 treatment. Blood-to-brain transport of [³H]atorvastatin (A), [³H]pravastatin (B), and [³H]rosuvastatin (C) were measured by the in situ brain perfusion approach. Animals were treated with BMP-9 (1 μg/kg, i.p.; 6-hour treatment) in the presence and absence of LDN193189 (10 mg/kg, i.p.; 1-hour pretreatment) and perfused with equal concentrations of radiolabeled statins (0.013 μM total concentration). Each experiment was conducted in the presence and absence of FEX (100 μM) to confirm specificity of Oatp-mediated transport. At the conclusion of the experiment, concentrations of each currently marketed statin were measured in cerebral cortex, hippocampus, and cerebellum. Results are expressed as mean ± S.D. of six animals per time point. Asterisks represent data points that were significantly different from control animals (*p < 0.05; **p < 0.01).