Vasopressin Synthesis by the Magnocellular Neurons is Different in the Supraoptic Nucleus and in the Paraventricular Nucleus in Human and Experimental Septic Shock

Abstract

Impaired arginine vasopressin (AVP) synthesis and release by the neurohypophyseal system, which includes the neurohypophysis and magnocellular neurons of the paraventricular and supraoptic nuclei, have been postulated in septic shock, but changes in this system have never been assessed in human septic shock, and only partially experimentally. We investigated AVP synthesis and release by the neurohypophyseal system in 9 patients who died from septic shock and 10 controls, and in 20 rats with fecal peritonitis-induced sepsis and 8 sham-operation controls. Ten rats died spontaneously from septic shock, and the others were sacrificed. In patients with septic shock, as in rats that died spontaneously following sepsis induction, AVP immunohistochemical expression was decreased in the neurohypophysis and supraoptic magnocellular neurons, whereas it was increased in the paraventricular magnocellular neurons. No significant change was observed in AVP messenger RiboNucleic Acid (mRNA) expression assessed by in situ hybridization in either paraventricular or supraoptic magnocellular cells. This study shows that both in human and experimental septic shock, AVP posttranscriptional synthesis and transport are differently modified in the magnocellular neurons of the supraoptic and paraventricular nuclei. This may account for the inappropriate AVP release in septic shock and suggests that distinct pathogenic mechanisms operate in these nuclei.

Changes in CRH and ACTH Synthesis during Experimental and Human Septic Shock

“…Whole brains and pituitary glands were removed immediately after animal sacrifice by neck dislocation, and fixed by immersion in 10% formalin. Brain samples were processed as previously described [14]. Briefly, after embedding in paraffin, serial sections of 4 µm were performed (Leica® microtome) until the region of interest was reached.…”

“…Immunohistochemistry was performed on deparaffinised formalin-fixed sections using an indirect ABC-peroxidase method revealed with 3-3′diaminobenzidine (DAB) or amino-ethyl-carbazol (AEC) as chromogenes [14]. For homogeneity of labelling, immunohistochemistry was performed using an automated IHC slide-staining system (NexES® IHC Full system, Ventana Medical Systems, Tucson, AZ, USA).…”

“…In situ hybridization was performed using a 200 bp rat vasopressin cDNA probe (gift from Dr C Rabadan-Diehl, Bethesda, MD, USA) and 1 kb rat CRH cDNA probe (gift from Dr Mayo, Evanston, IL, USA) as described previously [14]. Briefly, sense and antisense probes were synthesized from linearized plasmids using digoxigenin-UTP (Roche, France) and riboprobe combination system (Promega, France).…”

Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock*

“…In patients with septic shock, the presence of low-circulating AVP levels, unaltered clearance of AVP (14), and depletion of neurohypophyseal vesicles (14,15) support a central origin. Altered baroregulation or osmoregulation are the most plausible factors of central AVP deficiency (16).…”

Neuroanatomy of Sepsis-Associated Encephalopathy

“…Sepsis is associated with multiple neuroendocrine disorders [23,25,[31][32][33][34][35]. While the initial stage of sepsis is marked by increased secretion of pituitary hormones notably in response to a decreased sensitivity in peripheral hormonal receptors, prolonged sepsis is characterized by a decrease in pituitary hormone release [36].…”