Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia.
We have tested the hypothesis that nitric oxide (NO) arising from inducible nitric oxide synthase (iNOS) plays a role in hypothermia during endotoxemia by regulating vasopressin (AVP) release. Wild-type (WT) and iNOS knockout mice (KO) were intraperitoneally injected with either saline or Escherichia coli lipopolysaccharide (LPS) 10.0 mg/kg in a final volume of 0.02 mL. Body temperature was measured continuously by biotelemetry during 24 h after injection. Three hours after LPS administration, we observed a significant drop in body temperature (hypothermic response) in WT mice, which remained until the seventh hour, returning then close to the basal level. In iNOS KO mice, we found a significant fall in body temperature after the fourth hour of LPS administration; however, the hypothermic response persisted until the end of the 24 h of the experiment. The pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Et-Tyr2, Val4, Arg8-Vasopressin, an AVP V1 receptor antagonist (10 microg/kg) administered intraperitoneally, abolished the persistent hypothermia induced by LPS in iNOS KO mice, suggesting the regulation of iNOS under the vasopressin release in this experimental model. In conclusion, our data suggest that the iNOS isoform plays a role in LPS-induced hypothermia, apparently through the regulation of AVP release.
Saia
Rafael S
RS
Departamento de Enfermagem Geral e Especializada, Escola de Enfermagem de Ribeirão Preto/USP, 14040-902- Ribeirão Preto, SP, Brazil.
Carnio
Evelin C
EC
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000235:genetics*; D019446:Endotoxemia / Q000201:enzymology*; D004926:Escherichia coli; D006605:Hibernation / Q000187:drug effects / Q000235:genetics*; D006727:Hormone Antagonists / Q000494:pharmacology; D007036:Hypothermia, Induced; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage
D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D008070:Lipopolysaccharides; D009566:Nitrates; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D012965:Sodium Chloride; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D052247:Nitric Oxide Synthase Type II