A role for endothelin in the maintenance of post-ischaemic renal failure in the rat

• Published in: The Journal of physiology 1991-12, Vol.444 (1), p.513-522
• Main Authors: LOPEZ-FARRE, A, GOMEZ-GARRE, D, BERNABEU, F, LOPEZ-NOVOA, J. M
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - physiopathology; Animals; Antibodies; Biological and medical sciences; Endothelins - blood; Endothelins - immunology; Endothelins - physiology; Ischemia - complications; Kidney - blood supply; Kidney - physiopathology; Kidney Glomerulus - metabolism; Kidney Glomerulus - physiopathology; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Platelet Activating Factor - metabolism; Platelet Activating Factor - physiology; Rats; Rats, Inbred Strains; Renovascular diseases; Vasoconstriction
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1991.sp018891

1. Endothelin (ET) has been shown to reduce glomerular filtration rate (GFR) and renal blood flow (RBF) and may therefore be a possible mediator of the reduction of GFR and RBF observed in post-ischaemic acute renal failure. 2. We infused a specific ET antibody, i.v., for 1 h before and 1 h after a 60 min period of renal ischemia by clamping the renal artery, and observed the changes in renal function (acute clearance and long-term metabolic cage studies) compared with rats infused with non-immune rabbit serum. 3. In acute and long-term studies, better renal function, as judged by GFR and RBF was observed in rats treated with the ET antibody. Furthermore, ischaemic rats showed higher levels of plasma immunoreactive ET (7.02 +/- 1.17 pg ET (ml plasma)-1; mean +/- S.E.M.) than normal rats where it was undetected. 4. We previously reported that glomeruli and renal platelet-activating factor (PAF) production were increased after renal ischaemia. So, we studied the possible relationship between ET and glomeruli or renal PAF production in post-ischaemic acute renal failure. 5. Glomeruli from ischaemic rats produced greater amounts of PAF than glomeruli from normal or anti-ET antibody-treated ischaemic rats. In addition, total renal PAF production was higher in ischaemic-untreated than in non-ischaemic or anti-ET-treated rats. Glomeruli incubated with 10(-7) M-endothelin produced much more PAF than those incubated in control conditions (138.4 +/- 10.5 vs. 80.2 +/- 9.4 pg PAF (mg protein)-1; means +/- S.E.M.; n = 10). 6. In conclusion, the present study suggests that endothelin plays a role in the persistent renal vasoconstriction that characterizes post-ischaemic acute renal failure. In addition, the observed increase in glomerular PAF production after renal ischaemia may be due to the action of endothelin.