(A–C) Reversal of low renal perfusion in sickle mice by infusion of bosentan. Echo-Doppler measurements of (A) CO and (B) RBF velocity in the renal artery at steady state (white bars) and after H/R in SAD and WT mice before (black bars) and 10 minutes after infusion of bosentan (gray bars). H/R-induced vasoocclusive (VOC) events were associated with blunted CO and significant decreases in mean RBF velocity in SAD mice only. Acute infusion of bosentan restored 50% of the initial loss in RBF velocity within 10 minutes, whereas saline had no effect (not shown). n = 13. *P < 0.05 versus SAD at steady state; **P < 0.01 versus SAD at steady state; ^#P < 0.05 versus SAD before bosentan infusion. (C) Representative RBF waveforms in WT and SAD mice at steady state and after H/R followed by acute infusion of saline or bosentan. End-diastolic and time-averaged mean velocities were lower in saline-treated SAD mice after H/R than in normoxic WT and SAD mice. Acute ETRA restored end-diastolic and time-averaged mean velocities. (D and E) Prevention of H/R-induced renal hypoperfusion in SAD mice treated for 2 weeks with bosentan. (D) CO and (E) mean RBF velocity were unchanged in bosentan-treated SAD mice, whereas mean RBF velocity decreased by 50% in vehicle-treated SAD mice. All data are means ± SEM from n = 2 experiments. n > 10. ***P < 0.001 versus SAD at steady state; ^##P < 0.01 versus vehicle-treated SAD in H/R.