Thermoregulation during endotoxemia in mice lacking inducible nitric oxide synthase: Involvment of the arginine‐vasopressin

Background We have tested the hypothesis that nitric oxide (NO) arising from inducible nitric oxide synthase (iNOS) plays a role in hypothermia during endotoxemic shock, by regulating vasopressin (AVP) release. Methods and results 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 hours after LPS administration. One hour after LPS administration we observed a significant drop in body temperature (hypothermic response) in WT, which remained until the eighth hour after LPS injection, returning the close to the basal level. In iNOS KO mice, we found a significant fall in body temperature after the first hour of LPS administration, however the hypothermic response persisted until the end of the twenty‐four hour of experiment. The pre‐treatment with (b‐mercapto‐b,b‐cyclopentamethylenepropionyl1, O‐Et‐Tyr2, Val4, Arg8‐Vasopressin), an AVP V1 receptor blocker (10 μg/kg) administered i.p., abolished the persistent hypothermia induced by LPS in iNOS KO mice, suggesting the regulation of iNOS under the vasopressin release in this patophysiological model. Conclusion In conclusion, our data indicate that the inducible NOS isoform plays an inhibitory role in AVP release during endotoxemia, which seems to be critical for the thermoregulation during this pathophysiological state. Clinical Pharmacology & Therapeutics (2005) 77 , P9–P9; doi: 10.1016/j.clpt.2004.11.037