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

Abstract

SUMMARY1. 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 ischaemia 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)-'; 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.

Endothelin and endothelium‐derived relaxing factor control of basal renovascular tone in hydronephrotic rat kidneys.

“…In agreement with our observations, L6pez-Farre, Gomez-Garre, Bernabeu & Lopez-Novoa (1991) demonstrated an increase in both glomerular filtration rate (GFR) and RBF in rats treated with ET antibodies. However, their results are difficult to compare with ours, as Lopez-Farre et al did not quantify these ET effects on rat kidneys under baseline conditions.…”

Acute Renal Toxic Effect of Amiodarone in Rats

“…One day before start of treatment, the urine free of food and faeces, was collected into graduate recipients containing 100 ml of 0.1% sodium azide (to minimize the bacterial contamination) and 1 ml of mineral oil (to prevent evaporation) (Ló pez-Farré et al 1991). A blood sample (150 ml) was also collected from the caudal vein to determine plasma creatinine concentration.…”

Molecular Pharmacology and Pathophysiological Significance of Endothelin

“…Administration of an antibody to endothelin-1 before renal artery clamping in rats has been shown to prevent the increase in periglomerular arteriolar resistance and the reduction in single nephron glomerular filtration rate that occur for up to 48 hr following clamping (178). The histological charges that accompany proximal renal tubular necrosis were also shown to be prevented by endothelin-1 antibody in the rat renal ischemia model (176,179). An inhibitor of ECE-1, phosphoramidon, was also effective in preventing ischemia-induced ARF in animal models (180).…”