This study evaluated the usefulness of a non-selective and selective blockade of cyclooxygenases (COX) 1 and 2 with aspirin and Celecoxib, respectively, in moderating the haemodynamic responses over the first 2 h of reperfusion after an ischaemic challenge to the kidney. The role of nitric oxide (NO) in this setting was investigated using NCX4016 (Keeble et al. 2001), a combined non-selective COX inhibitor and NO donor.

All procedures were performed under UK Home Office licences. Groups of male Wistar rats (n = 5-7, 250-350g) received vehicle, aspirin (100 mg kg^-1 day^-1), NCX4016 (100 mg kg^-1 day^-1) or Celecoxib (10 mg kg^-1 day^-1), orally for 14 days. On day 14 the rats were anaesthetised with sodium pentobarbitone (60 mg kg^-1, I.P., 3 mg I.V. when necessary). Cannulae were placed in the femoral artery to measure blood pressure and femoral vein for the infusion of normal saline at 3 ml h^-1. The left kidney was exposed, the renal capsule removed and laser-doppler flowmeter microprobes were inserted to a depth of 1.5 mm (cortex) and 5 mm (medulla) with 100 perfusion units (PU) equivalent to 1 V. After 1 h, 2 min baseline readings were taken. The renal artery was clamped for 30 min. Upon clamp removal, 2 min readings were taken every 10 min for 90 min and the animal was killed with an anaesthetic overdose. Means ± S.E.M. were compared using ANOVA and significance taken at P < 0.05.

The cortical perfusion responded similarly to a period of ischaemia in the aspirin, Celecoxib and vehicle treated groups. PU decreased from basal levels of 136 ± 20 PU by at least 35 % 10 min after the ischaemic challenge and remained depressed. The NCX4016 treated group however, initially decreased from 160 ± 22 PU but recovered, finishing at 110 % of baseline, which was different from the response in the vehicle group (P < 0.05). Medullary responses of the Celecoxib and vehicle groups to the period of ischaemia showed a similar pattern, that is basal levels were 57 ± 5 and 90 ± 12 PU and fell 50 % after 10 min and increased to 60 % of basal after 90 min. In the Aspirin treated group, after an initial decrease to 75 % of basal levels (84 ± 10 PU), it increased to around 85 %. The NCX4016 treated group also displayed a significantly different (P < 0.05) response to the vehicle in that it fell to 70 % of 84 ± 15 PU and returned to baseline value at 90 min.

These results indicate that in both the cortex and medulla a combination of COX inhibition and NO release by NCX4016 had a beneficial effect on renal vasculature in comparison to selective COX2 inhibition.