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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kato
A
A
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hishida
A
A
D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D019332:Endothelin-1 / Q000502:physiology*; D016232:Endothelins / Q000276:immunology; D006439:Hemodynamics; D007211:Indoles / Q000494:pharmacology; D007444:Inulin / Q000378:metabolism; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000150:complications*
D000911:Antibodies, Monoclonal; D001381:Azepines; D019332:Endothelin-1; D016232:Endothelins; D007211:Indoles; C079574:FR 139317; D007444:Inulin