Early treatment with MEK1/2 inhibitor prevents delayed upregulation of ET
- and 5-HT
-mediated vasoconstriction and receptor protein expression in cerebral arteries after SAH. (A-B) Concentration-contraction curves obtained at 3 days after sham-operation or SAH for basilar arteries stimulated with cumulative doses of ET-1 (A) or 5-CT (B). Shown are data for sham-operated rats (Sham), SAH rats treated with U0126 at 6 h, 12 h and 24 h after SAH (SAH + U0126) and SAH rats treated with vehicle at similar time points (SAH + vehicle). All SAH rats included had prolonged acute CBF drops. Data are mean ± s.e.m as percent of 63 mM K+-induced contractions. Stars indicate significant differences between sham and SAH-induced animals as determined by two-way ANOVA (*** p < 0.001, ** p < 0.01, * p > 0.05). Crosses indicate significant differences between U0126- and vehicle-treated SAH rats as determined by two-way ANOVA (+++ p < 0.001). (C-D): Immunoblots of ETB and 5-HT1B receptor expression and actin levels (loading control) in cerebral artery tissue from sham-operated rats and SAH rats with prolonged acute CBF drops treated with U0126 or vehicle. The experiment was repeated three times and one representative immunoblot for each receptor type is shown.