Fig. 6.

Selective inhibition of COX-1 or COX-2 prevents PHT in COX-2^−/− and COX-1^−/− mice, respectively. B6;129P2-Ptgs1^tm1 (COX-1^−/−) (A–C) and B6;129P2-Ptgs2^tm1 (COX-2^−/−) (D–F) mice were given either DMSO (vehicle control) 2 mg·kg⁻¹·day⁻¹ ip NS-398 or 20 mg/kg ip SC560 prior to and following partial PVL or sham surgery. DMSO and 2 mg/kg NS398 was given daily for 7 days, and SC560 was given at 20 mg/kg every 48 h for 7 days. During this time total urine output was collected. After 7 days the abdominal aortic flow (A and D) and splenic pulp pressure (B and E) were measured and the urine was analyzed for the prostacyclin metabolite 2,3-dinor-6-keto-PGF_1α. Histograms show data for 7-day sham-DMSO since there was minimal effect of 2 mg/kg NS398 or 20 mg/kg SC560 in shams (A–F). In both COX-1^−/− and COX-2^−/− mice abdominal aortic flow, splenic pulp pressure, and 7-day urine 2,3-dinor-6-keto-PGF_1α were increased 7 days following PVL (shaded bars) compared with 7-day shams (open bars). Treatment with 2 mg/kg NS398 (hatched bars) prevented this increase in 7-day PVL-COX-1^−/− mice, whereas treatment with 20 mg/kg SC560 had no effect. In contrast, abdominal aortic flow, splenic pulp pressure, and urine 7 days 2,3-dinor-6-keto-PGF_1α were significantly reduced in 7-day PVL-COX-2^−/− mice treated with 20 mg/kg SC560 but remained elevated in mice treated with 2 mg/kg NS398. Data represents means ± SE; n = 5 per group.