Role of nitric oxide in thermoregulation during septic shock: involvement of vasopressin

Abstract

We tested the hypothesis that the nitric oxide (NO) pathway in the central nervous system (CNS) plays a role in hypothermia, as well as in the febrile response during experimental septic shock, by regulating vasopressin (AVP) release. Experiments were performed on male Wistar rats treated with NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase (NOS) inhibitor, injected intracerebroventricularly (250 microg/1 microl) 30 min before lipopolysaccharide (LPS) 1.5 mg/kg i.v. injection. One hour after LPS administration we observed a significant drop in body temperature (hypothermic response), followed by a temperature increase after the second hour (febrile response), which remained until the end of the experiment. Increased plasmatic AVP levels were concomitantly observed during hypothermia, nearly returning to basal levels during the febrile phase. When L-NAME was administered with LPS, plasmatic AVP concentrations remained high throughout the experiment, hypothermia was accentuated and the febrile response was abolished. Additionally, pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Et-Tyr2, Val4, Arg8-vasopressin, an AVP V1 receptor blocker (10 microg/kg) administered i.v., reduced hypothermia and exacerbated the febrile response to endotoxin. In conclusion, our data indicate that the central NO pathway plays an inhibitory role in AVP release during experimental septic shock, which seems to be critical for the thermoregulation during this pathophysiological state.

Interleukin-6 activates arginine vasopressin neurons in the supraoptic nucleus during immune challenge in rats

“…This release was maintained at a high level Յ6 h post-LPS and was coupled to a decrease in diuresis. These results corroborate precise previous data reporting 1) an increase in c-fos mRNA expression in rat SON 2 h after ip LPS that vanished 6 h later (41,42), 2) an increase in Fos protein expression in rat AVP neurons 2 h after LPS ip injection (35,51), and 3) an increase in rat plasma [AVP] from 1 to 3 h after LPS (19,25). The differences in the kinetics of changes between our results and those of the literature may be due to the differences in doses and routes of LPS injection.…”

“…Plasma AVP release was quantified in control handled (n ϭ 4/time posttreatment), PBS-treated (n ϭ 4/time posttreatment), and LPStreated rats (n ϭ 63) killed at 1, 2, 3, 6, and 18 h posttreatment (for LPS, n is equal to 20,19,8,8, and 8, respectively according to time groups). All rats were decapitated to collect blood in chilled tubes coated with heparin (CML, Nemours, France).…”

“…Because LPS injection has been shown to induce an increase of plasma AVP concentration in adult rats (18,25), we studied the evolution of the electrical activity of AVP neurons in response to a LPS peripheral injection in anesthetized adult rats. Only AVP neurons initially displaying a phasic activity were considered.…”

“…AVP neurons of the paraventricular (PVN) and supraoptic (SON) nuclei are well known to be activated in response to osmotic and volume dehydrations and to decrease in blood pressure (26,37,46). AVP neurons can also be activated in response to peripheral inflammation, as attested by the increase in AVP circulating levels after peripheral injection of lipopolysaccharide (LPS) in rat (18,24,25) and sheep (36) and intense nuclear c-fos immunoreactivity in AVP containing magnocellular neurons of the rat SON (35,40) and PVN (20,50).The mechanisms that are responsible for the activation of AVP neurons in response to an endotoxin challenge need to be elucidated. Potentially, dysregulation in water homeostasis caused by LPS-induced fever and inflammation could be responsible for AVP neuron activation.…”

Thermoregulation and Vasopressin Secretion during Polymicrobial Sepsis

“…AVP is believed to be an endogenous antipyretic agent [4,12,13,32] . An elevation in plasma AVP levels has been associated with a more intense period of hypothermia during endotoxemia [33] . In this study, hypothermia was also temporally correlated with an increase in plasma AVP levels, suggesting a role in Tb regulation for this hormone during polymicrobial sepsis.…”