AIM: This study investigated the effect of a selective A(1)-adenosine receptor (A(1)-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 microg/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 A(1)-AR contributes to the early development of renal ischaemia/reperfusion injury.
AIM: This study investigated the effect of a selective A(1)-adenosine receptor (A(1)-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 microg/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 A(1)-AR contributes to the early development of renal ischaemia/reperfusion injury.
Authors: Z Lin; P Yin; S Reierstad; M O'Halloran; V J S Coon; E K Pearson; G M Mutlu; S E Bulun Journal: Oncogene Date: 2009-11-23 Impact factor: 9.867