Amelioration of post-ischaemic renal injury by contralateral uninephrectomy: a role of endothelin-1.

Abstract

Previous studies showed that unilateral renal damage is attenuated by prior contralateral uninephrectomy (Nx) in ischaemia-induced acute renal failure (ARF). Since renal ischaemia increases endothelin-1 (ET-1) production in the kidney, we examined whether the alteration of renal ET-1 content may contribute to the nephrectomy-induced attenuation of renal injury. Ischaemic renal injury was provoked by 60-min left renal artery occlusion (RAO). Removal of the right kidney was performed just before RAO in the Nx group. Forty-eight hours after release of the clamp, renal ET-1 content was measured in both non-nephrectomized and unilaterally nephrectomized rats. We also examined the effects of a selective ET(A) receptor (FR139317) and monoclonal ET antibody (AwETN40) on the RAO-induced changes in renal haemodynamics at 2 and 48 h after RAO respectively. The plasma concentration of ET-1 did not change in the two groups of ARF rats, but the cortical content of ET-1 increased to a lesser extent in Nx animals after ischaemia. Prior removal of the right kidney significantly facilitated the percentage recovery of left renal blood flow (RBF) during the first 2 h after release of the clamp. The percentage recovery of inulin clearance (Cin) by the kidney was also significantly better in Nx than sham-Nx rats at 48 h after RAO. Continuous administration of FR139317 (50 mg/kg/day) using osmotic minipumps for 3 days significantly attenuated exogenous ET-1-induced decrease in Cin and RBF. Infusion of FR139317 restored the decrease in RBF to control values during first 2 h in sham-Nx rats. However, FR139317 and AwETN40 did not ameliorate the RAO-induced decline of Cin in sham-Nx or Nx rats at 2 and 48 h after ischaemia respectively. Contralateral uninephrectomy prior to ischaemia-induced ARF attenuated the increase in cortical ET-1 content and subsequent renal response to ischaemic injury. This beneficial effect of unilateral nephrectomy, however, was not mediated through well-preserved RBF due to reduced intrarenal ET-1 action.