Title of article :
Effect of Endothelin-A Receptor Blockade on the Early Phase of Ischemia/Reperfusion- Induced Acute Renal Failure in Anesthetized Rats
Author/Authors :
Shid Moosavi, S.M Deparment of Physiology, University College Cork , Barmaki, B Deparment of Physiology, University College Cork , Geramizadeh, B Deparment of Physiology, University College Cork , Fallahzadeh, M. H Deparment of Physiology, University College Cork , Johns, E. J Deparment of Physiology, University College Cork
Abstract :
Background: Previous studies have shown increases in endothelin
(ET) concentration of plasma and renal tissues in acute
renal failure (ARF). ET has a potent vasoconstrictor effect,
through binding with its ETA receptors, and may play some
roles in renal hemodynamic dysfunction in ARF.
Objective: To examine the beneficial effect of a selective
ETA-receptor antagonist on renal dysfunction and tissue damage
occurring during the early phase of ischemia/reperfusioninduced
ARF.
Methods: Pentobarbital anesthetized rats were prepared for
the measurement of blood pressure and renal function. A 0.5
hr clearance period was taken as control period, followed by 1
hr, and then a 4 hr experimental clearance period was taken. In
ischemia/reperfusion (I/R) group, 30 min after the end of the
control clearance period, renal ischemia was induced by bilateral
renal artery clamping for 30 min. In drug-treated (I/R+D)
group, a selective ETA-receptor antagonist (UK-350,926) was
infused iv at 50 mg/kg/min for 30 min before and 2 hr following
occlusion of renal arteries. There was also a shamoperated
group.
Results: In I/R group, renal ischemia lowered creatinine clearance
(CCr) by 76% (p<0.001), but elevated urine flow rate (V0)
by 2.9-fold (p<0.01) and absolute Na+ excretion (UNaV0) by
3.2-fold (p<0.05) during the 4 hr reperfusion period as compared
to their own control values. In I/R+D group, V0 and
UNaV0 did not change significantly during the 4 hr experimental
period, but the amount of decrease in CCr was equal to that
of I/R group. Histological examination showed a mild degree
of tissue damage in the cortex of I/R group but not in I/R+D
and sham groups.
Conclusion: Administration of the ETA-receptor antagonist
does not prevent the fall of glomerular filtration, but it does
ameliorate the damage of renal tissue and tubular reabsorption
of Na+ and water during 4 hrs of reperfusion following the
ischemic challenge.
Keywords :
Acute renal failure , ischemia/reperfusion , ETAreceptor antagonist
Journal title :
Astroparticle Physics
