Involvement of nitrergic and opioidergic systems in the hypothermia induced by cholestasis in rats

Cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli and decreased febrile response to lipopolysaccharide. The present study was undertaken to determine if obstructive cholestasis was associated with abnormal thermoregulation under thermoneutral conditions.

Male Sprague-Dawley rats weighing 200-250g were randomly divided into 21 groups. Three sets of seven groups were unoperated control, sham-operated and bile duct-ligated rats. The groups of unoperated control, sham-operated and bile duct-ligated rats were treated with daily administration of isotonic saline solution, N(omega)-nitro-l-arginine methyl ester (l-NAME) (3, 10, or 20mg/kg), naltrexone (10 or 20mg/kg) or aminoguanidine (150mg/kg). Body temperatures were measured before and 1, 3, 5 and 7 days after the surgery.

Bile duct-ligated rats had lower body temperature than sham-operated animals at 3 (P<0.001) and 5 (P<0.01) days after surgery. l-NAME, a non-selective inhibitor of nitric oxide synthase (NOS) (10, 20mg/kg, i.p.) or aminoguanidine, a selective iNOS inhibitor (150mg/kg, i.p.), completely reversed this hypothermia (P>0.05). Naltrexone, a non-selective opioid antagonist (20mg/kg, i.p.), also completely corrected this hypothermia (P>0.05). There was a drop in temperature in the first day after the surgery in sham and BDL groups compared to unoperated controls, which was significant in some groups demonstrating the effect of surgery and anesthetic drugs on the body temperature.

Cholestatic rats show impaired thermoregulation suggesting the involvement of nitrergic and opioidergic systems.