Losartan (Los) did not improve recovery of postischemic limb appearance, use, perfusion, or tissue survival. Oral losartan throughout the recovery period and for either 3 days or 8 wk before severe surgery (A–D) or 8 wk before mild surgery (E–H) failed to improve recovery of the postsurgery hindlimb of Cx40−/− male mice. Recovery of hindlimb appearance (A, E) and hindlimb use (B, F) after both surgery types was not different (rank sum test) between losartan-treated and untreated Cx40−/− male mice [appearance data: severe surgery, Cx40−/− no losartan, n = 13, 3-day losartan, n = 7, 8-wk losartan, n = 9; mild surgery: no losartan, n = 10, 8-wk losartan, n = 11; use data, severe surgery: no losartan, n = 11, 3-day losartan, n = 7, 8-wk losartan, n = 9; mild surgery: no losartan, n = 10, 8-wk losartan, n = 11]. C and G: recovery of distal limb perfusion over 14 days was minimal after severe surgery in all Cx40−/− mice (C), irrespective of losartan treatment; in contrast, whereas perfusion improved significantly (†) over time after mild surgery in untreated Cx40−/− mice (†, ANOVA, P = 0.00185), it did not improve in losartan-treated (P = 0.113) Cx40−/− male mice subjected to the mild surgery. Thus recovery of perfusion by day 14 was greater in untreated than treated mice at day 14 (*P < 0.01, t-test). D and H: losartan-treated Cx40−/− male mice were, if anything, more likely to suffer tissue necrosis, although survival times were not different even for 3-day losartan-treated mice (no losartan: 10 ± 2 days and 3-day losartan: 6 ± 2 days, P = 0.104; severe surgery: no losartan, n = 11, 3-day losartan, n = 7, 8-wk losartan, n = 9; mild surgery: no losartan, n = 10, 8-wk losartan, n = 11).