Effects of a neuronal nitric oxide synthase inhibitor on lipopolysaccharide-induced fever

It has been demonstrated that nitric oxide (NO) has a thermoregulatory acti on, but very little is known about the mechanisms involved. In the present study we determined the effect of neuronal nitric oxide synthase (nNOS) inh ibition on thermoregulation. We used 7-nitroindazole (7-NI, 1, 10 and 30 mg /kg body weight), a selective nNOS inhibitor, injected intraperitoneally in to normothermic Wistar rats (200-250 g) and rats with fever induced by lipo polysaccharide (LPS) (100 mu g/kg body weight) administration. It has been demonstrated that the effects of 30 mg/kg of 7-NI given intraperitoneally m ay inhibit 60% of nNOS activity in rats. In all experiments the colonic tem perature of awake unrestrained rats was measured over a period of 5 h at 15 -min intervals after intraperitoneal injection of 7-NI. We observed that th e injection of 30 mg/kg of 7-NT induced a 1.5 degrees C drop in body temper ature, which was statistically significant 1 h after injection (P<0.02). Th e coinjection of LPS and 7-NI was followed by a significant (P<0.02) hypoth ermia about 0.5 degrees C below baseline. These findings show that an nNOS isoform is required for thermoregulation and participates in the production of fever in rats.