Effect of endothelin antagonists on the renal haemodynamic and tubular responses to ischaemia-reperfusion injury in anaesthetised rats.
In this investigation we have evaluated whether blockade of endothelin receptors influenced the renal haemodynamic and excretory responses to a period of ischaemia and reperfusion in the anaesthetised rat. The renal artery was occluded for 30 min and renal haemodynamic and excretory function followed for 90 min of reperfusion while either saline, the non-selective endothelin 1 receptor (ET(A)/ET(B)) antagonist SB209670 or the selective ET(A) receptor antagonist UK-350,926 was infused. In the post-ischaemic period, renal cortical and medullary perfusions were reduced by 40-50 %. When SB209670 was administered (30 micro g kg(-1) min(-1) I.V.) for 30 min before, during and for 90 min after renal artery occlusion, cortical and medullary perfusions returned to baseline levels, responses different from those obtained during saline infusion (both P < 0.05). In the presence of UK-350,926 (30 micro g kg(-1) min(-1) I.V.), perfusion in the medulla returned to baseline on clamp removal whereas that in the cortex remained depressed (P < 0.05). Renal ischaemia for 30 min decreased glomerular filtration rate during reperfusion and increased urine flow and sodium excretion 5- to 15-fold. UK-350,926 (30 micro g kg(-1) min(-1) I.V.) reduced (P < 0.05) fluid excretion prior to ischaemia but during reperfusion, glomerular filtration rate returned to basal levels and there were progressive increases in fluid excretion which were smaller compared to the saline-treated group (all P < 0.05). The ischaemic challenge may cause release of endothelin, which acts on ET(B) receptors in the cortex and ET(A) receptors in the medulla to decrease perfusion. The blunted natriuresis and diuresis during blockade of ET(A) receptors may result from either a vascular or tubular action of endothelin.
Ajis
Adam
A
Department of Physiology, The Medical School, Birmingham B15 2TT, UK.
Bagnall
Nigel M
NM
Collis
Michael G
MG
Johns
Edward J
EJ
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D007189:Indans / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D065130:Endothelin A Receptor Antagonists; D007189:Indans; D044022:Receptor, Endothelin A; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-