Proceedings of The Physiological Society
Trinity College Dublin (2003) J Physiol 551P, PC38
Effect of non-selective cyclooxygenase inhibition on renal function in ischaemia-reperfusion injury in the anaesthetised normotensive and hypertensive rat
Sarah Knight and E.J. Johns
Department of Physiology, University College Cork, Eire
Prostaglandins have a regulatory role in the normal functioning of the kidney, but their involvement in the renal response to ischaemia is little understood. We investigated the effect of non-selective inhibition of cyclooxygenase (COX) enzymes on renal function up to 2.5 h after a period of ischaemia in Wistar and stroke-prone spontaneously hypertensive rats (SPSHRs).
Two groups of male Wistar and two groups of male SPSHRs (n = 5-7, 250-350 g) received polyethylene glycerol vehicle or aspirin (53.8 mg kg-1 day-1) orally for 7 days. On day 7 the rats were anaesthetised with chloralose-urethane (12 and 180 mg ml-1; 1 ml I.P. initially, 0.05 ml I.V. when necessary). A tracheostomy was performed and cannulae were placed in the right femoral vein for the infusion of inulin (1.5 g (100 ml)-1 0.9 % saline; at 3 ml h-1) and anaesthetic, and in the right femoral artery for BP, heart rate monitoring and taking plasma samples. The left ureter was cannulated for the collection of urine and the rat was left to stabilise for 1-2 h. Two baseline collections of urine and plasma were taken, and a non-traumatic clamp was placed on the renal artery for 30 min. Further urine collections were taken at 15 and 30 min, and 1, 1.5 and 2 h, and plasma samples at 0 and 30 min and 1.5 h. Animals were humanely killed with an anaesthetic overdose. Data are means and S.E.M., and were compared using ANOVA, with significance taken at P ?le? 0.05.
The mean arterial pressure returned to near basal levels 2 h after the period of ischaemia in all groups. The vehicle-treated SPSHRs had the highest BP of 140-160 mmHg, the vehicle-treated Wistar group was at 120 mmHg, the aspirin-dosed SPSHRs was at 110 mmHg and the lowest BP at 90-100 mmHg was the aspirin-treated Wistar group, thus indicating that the inhibition of vasoconstrictor prostaglandins by aspirin counteracted the SPSHR's genetic predisposition to hypertension. The vasodilatory effect of aspirin was also apparent in the renal blood flow (RBF) data. In both aspirin-treated groups the RBF was between 50 and 65 ml min-1 kg-1, which was significantly higher than both vehicle-treated groups, which were between 15 and 20 ml min-1 kg-1. The glomerular filtration rate (GFR) fell by at least 50 % in all groups after the ischaemic period, indicating that the inhibition of COX enzymes afforded little protection to GFR. However aspirin ameliorated the diuretic effect of ischaemia seen in the vehicle-treated groups, as the aspirin-treated groups had significantly lower urine flows. The beneficial effect of non-selective COX inhibition was also indicated by the decreased natriuretic effect of the aspirin-treated groups in comparison to the vehicle. These results suggest COX inhibition could have a protective effect during ischaemia-reperfusion injury.
Where applicable, experiments conform with Society ethical requirements