Orexin-A improves ischaemia/reperfusion-induced acute renal failure

Abstract

This study investigated the effect of orexin-A on the renal dysfunction and histological damage induced by ischaemia/reperfusion at an early stage. Pentobarbital anaesthetised rats were prepared for measuring renal functional variables. Ischaemia was induced by bilateral renal artery clamping for 30 min followed by a 1-h reperfusion period. In orexin-treated rats, it was infused (i.v.) at 500 pmol kg−1 min−1 from starting pre-ischaemic (pretreatment) clearance period. The left kidney was examined using light microscopy. The renal ischaemic challenge resulted in major histological 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 orexin-treated rats, the histological 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. Orexin-A exhibited a renoprotective effect against ischaemia/reperfusion-induced lesions probably via inhibition of post-ischaemic intrarenal vasoconstriction.