Early renal post-ischaemic tissue damage and dysfunction with contribution of A1-adenosine receptor activation in rat


Dr Seyed Mostafa Moosavi, Department of Physiology, The Medical School, Shiraz University (Medical Sciences), Shiraz 71365-1689, Iran. Email: mmoosavi@sums.ac.ir


Aim:  This study investigated the effect of a selective A1-adenosine receptor (A1-AR) antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), on the renal dysfunction and histological damage induced by ischaemia/reperfusion at an early stage.

Methods:  Pentobarbital anaesthetised rats were prepared for measuring renal functional variables. Ischaemia was induced by bilateral renal artery clamping for 30 min followed by a 4 h reperfusion period. In DPCPX-treated rats, it was infused (i.v.) at 10 µg/kg per min before and after renal ischaemia. Both kidneys were examined using light and electron microscopy.

Results:  The renal ischaemic challenge resulted in major histological and ultrastructural damages, which were associated with decreased creatinine clearance, absolute potassium-excretion and effective free-water reabsorption, but increased fractional sodium-excretion and urine flow during reperfusion period. In DPCPX-treated rats, the histological and ultrastructural damage to the kidneys was improved along with the decrease in creatinine clearance and increase in fractional sodium-excretion being smaller, but the increase in urine flow being larger than those of the non-treated rats, while absolute potassium-excretion and effective free-water reabsorption were equal to those of the sham-operated rats.

Conclusion:  These findings suggest that endogenous activation of A1-AR contributes to the early development of renal ischaemia/reperfusion injury.