Fig. 4.

Brain accumulation of [³H]atorvastatin and [³H]pravastatin is determined by OATP-mediated transport at the BBB. Effect of an established OATP transport inhibitor (i.e., E3S on the uptake of [³H]atorvastatin and [³H]pravastatin into rat brain post-treatment was assessed by in situ brain perfusion studies). Accumulation of these drugs was measured in animals injected with BMP-9 (1 μg/kg, i.p.) in the presence and absence of LDN193189 (10 mg/kg, i.p.; 1-hour pretreatment), where animals were perfused for 5 minutes with E3S (100 μM) prior to perfusion with [³H]atorvastatin or [³H]pravastatin. Results are expressed as mean ± S.D. of six animals per treatment group. Data points that are significantly different are indicated as follows: **P < 0.01, relative to atorvastatin control; ΦΦP < 0.01, relative to pravastatin control; ωωP < 0.01, relative to atorvastatin uptake in BMP-9-treated animals; ΔΔP < 0.01, relative to pravastatin uptake in BMP-9-treated animals; φφP < 0.01, relative to atorvastatin uptake in LDN193189 + BMP-9-treated animals; χχP < 0.01, relative to pravastatin uptake in LDN193189 + BMP-9-treated animals; and θP < 0.05; θθP < 0.01, specific comparisons indicated by black lines.