Ischaemic preconditioning (IPC) protects the heart and kidneys against ischaemia-reperfusion (I/R) injury. It has been shown that
opioid receptor activation can mimic cardiac IPC. In a kidney model of I/R, a single dose of
morphine failed to mimic IPC. The aim of the present study was to determine the role of chronic
morphine (dependence) in protection against renal I/R injury. Male Wistar rats were treated with increasing doses of
morphine (20-30 mg/kg per day, s.c., for 5 days) to develop
morphine dependence (MD). Three weeks before the I/R procedure, the right kidney was removed. Ischaemia-
reperfusion injury was induced by clamping the left renal artery for 45 min, followed by 24 h reperfusion. Some MD rats were pretreated with
naloxone (5 mg/kg, s.c.). Twenty-four hours later,
creatinine and
sodium concentrations were measured in serum and urine, then
creatinine clearance (CCr) and the fractional excretion of
sodium (FE(Na)) were calculated. Blood
urea nitrogen (BUN) was measured only in serum samples. Kidneys were also assessed histologically for evidence of tissue injury. In the present study, MD decreased tissue injury (histological score), serum
creatinine and BUN levels, increased CCr and decreased FE(Na) after I/R. Pretreatment with
naloxone attenuated the protective effects of MD.
Morphine dependence did not have any significant effect on urine volume. In conclusion, it seems that
morphine dependence protects the kidney against I/R injury via
opioid receptor-dependent pathways. Further studies are required to clearly determine the mechanisms involved.