Effects of a neuronal nitric oxide synthase inhibitor on lipopolysaccharide-induced fever.
It has been demonstrated that nitric oxide (NO) has a thermoregulatory action, but very little is known about the mechanisms involved. In the present study we determined the effect of neuronal nitric oxide synthase (nNOS) inhibition on thermoregulation. We used 7-nitroindazole (7-NI, 1, 10 and 30 mg/kg body weight), a selective nNOS inhibitor, injected intraperitoneally into normothermic Wistar rats (200-250 g) and rats with fever induced by lipopolysaccharide (LPS) (100 microg/kg body weight) administration. It has been demonstrated that the effects of 30 mg/kg of 7-NI given intraperitoneally may inhibit 60% of nNOS activity in rats. In all experiments the colonic temperature 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 the injection of 30 mg/kg of 7-NI induced a 1.5 degrees C drop in body temperature, which was statistically significant 1 h after injection (P<0.02). The coinjection of LPS and 7-NI was followed by a significant (P<0.02) hypothermia 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.
Perotti
C A
CA
Departamento de Enfermagem Geral e Especializada, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Nogueira
M S
MS
Antunes-Rodrigues
J
J
Cárnio
E C
EC
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy*; D007191:Indazoles / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007191:Indazoles; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester