Rg. Evans et al., Renal haemodynamic effects of endothelin-1 and the ETA/ETB antagonist TAK-044 in anaesthetized rabbits, J HYPERTENS, 16(12), 1998, pp. 1897-1905
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective The aim of this study was to test the effects of exogenous endoth
elin-1 (ET-1) on regional kidney blood flow and renal function, and the ren
al haemodynamic effects of endogenous ET, in anaesthetized rabbits.
Methods ET-1 was infused into the left renal artery at 2 ng/kg/min for 30 m
in, then at 1 ng/kg/min. Cumulative doses of TAK-044 (0.1-3 mg/kg, i.v.) or
its vehicle were given at 30-min intervals. In other rabbits, an extracorp
oreal circuit was established to adjust renal arterial pressure (RAP) indep
endently of systemic arterial pressure (MAP). RAP was set at 65 mmHg, and e
ither TAK-044 (3 mg/kg, i.v.) or its vehicle was administered.
Results In the infused kidney ET-1 (2 ng/kg/min) reduced renal blood flow (
RBFprobe; 52 +/- 8%), cortical perfusion (37 +/- 7%), glomerular filtration
rate (GFR; 49 +/- 8%), urine flow (47 +/- 14%) and sodium excretion (49 +/
- 13%), but not medullary perfusion (5 +/- 6%). No effects of ET-1 on MAP o
r on the contralateral kidney were observed. TAK-044 dose-dependently rever
sed the effects of ET-1 on RBFprobe end cortical perfusion. TAK-044 also re
duced MAP (by up to 11 +/- 3%) and increased effective renal blood flow in
the contralateral kidney (by up to 46 +/- 27%). In the extracorporeal circu
it model, TAK-044 decreased MAP by 12 +/- 2% and RAP by 10 +/- 3%, and incr
eased RBF by 9 +/- 3%.
Conclusion Exogenous ET-1 reduces cortical more than medullary perfusion, a
nd reduces GFR without affecting net tubular sodium and fluid reabsorption.
TAK-044 antagonizes local renal vascular responses to ET-1. Endogenous ETs
appear to contribute markedly to resting renal vasomotor tone and MAP. J H
ypertens 1998, 16:1897-1905 (C) 1998 Lippincott Williams & Wilkins.