Thermoregulation and Vasopressin Secretion during Polymicrobial Sepsis

Abstract

Objective: We investigated the time course of thermoregulation, nitric oxide (NO) formation and hydroelectrolytic alterations, as well as mean arterial pressure and arginine vasopressin (AVP) secretion, in experimental sepsis induced by cecal ligation and puncture (CLP). Methods: Male Wistar rats submitted to CLP or a sham operation were divided into 4 groups, as follows: group 1, for survival rate evaluation for 24 h; group 2, for body temperature (Tb) analysis; group 3, for mean arterial pressure registration, and group 4, for blood collection and processing of the neurohypophysis and hypothalamic nuclei 0, 2, 4, 6 and 24 h after surgery. AVP levels and content were measured in plasma, neurohypophysis and the hypothalamic paraventricular and supraoptic nuclei. Results: Animals which underwent CLP showed high mortality, a progressive decrease in mean arterial pressure and an increase in plasma NO. Tb dropped during the first 4 h and showed a progressive increase 6 h after surgery. Plasma AVP levels increased immediately after CLP surgery and again at 6 h, before returning to basal levels at 24 h. This was followed by a depletion of neurohypophyseal AVP content at 4 h that continued until 24 h. AVP content in the supraoptic nucleus was elevated 24 h after CLP surgery, while in the paraventricular nucleus, an increase was observed at 6 h and 24 h. Conclusions: In the present study, laparotomy and hypotension may have been responsible for the increase in plasma AVP in the initial phase of polymicrobial sepsis, and this may have contributed to the observed hypothermia. Moreover, an apparently impaired replenishment of AVP content in the neurohypophysis, possibly due to increased NO formation, may explain the impaired AVP secretion in the late phase of severe sepsis.

Oxytocin Affects Nitric Oxide and Cytokine Production by Sepsis-Sensitized Macrophages

“…Differences in OXT content were also seen in the sham group, both in the neurohypophysis (p < 0.05) and PVN (p < 0.001), and may possibly be attributed to the nervous stimulation of the autonomic system caused by abdominal manipulation during surgery. Similar alterations had previously been seen by us for vasopressin [4]. Peritoneal macrophage cultures obtained from naive rats showed an intense response to the LPS immune challenge, as evidenced by high concentrations of inflammatory mediators in the culture medium.…”

“…The neurohypophyseal hormone content was diminished in the early phase and basal in the late phase. This secretion profile is very much similar to that previously seen for AVP in septic rats [4,25]. As NO levels increase progressively during sepsis, this mediator may play a role by affecting the hypothalamic-neurohypophyseal axis and blunting OXT secretion in the late phase of sepsis, as we also previously reported for AVP [25].…”

“…All experimental surgeries were started between 9:00 and 11:00 a.m.. Induction of severe sepsis was by a CLP model as previously described [4]. Briefly, rats were anesthetized with a short-acting anesthetic agent (tribromoethanol; 2.5%, 250 mg/kg i.p.…”

“…In the early phase, the levels of vasopressin (AVP) are increased, but in the late phase these are diminished. These temporal hormonal changes following the onset of sepsis are believed to be an attempt of the organism to normalize blood pressure that is decreased due to the production of inflammatory mediators like cytokines and nitric oxide (NO) [1,2,3,4]. …”

Vasopressin and Its Immune Effects in Septic Shock

“…When faced with dehydration and corresponding hypertonicity of extracellular fluid, vasopressin is released and blood concentrations rise to 10-20 pg/ml. Shock and hypotension initially induce greater release of posterior pituitary vasopressin stores resulting in increased blood vasopressin concentrations [4] of up to 100-500 pg/ml. Vasopressin levels decline rapidly after the initial release of vasopressin (at least in part because of depletion of stored vasopressin [5] ) to levels that are inappropriately low compared to similarly hypotensive patients who had cardiogenic shock [6][7][8] .…”