Insufficient Vasopressin Release From Adequate Pituitary Stores Contributes to Inappropriately Low Plasma Vasopressin Levels in the Acute Response to Septic Shock

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Inadequate endogenous vasopressin (eVP) levels have been well described in catecholamine resistant hypotension in the setting of septic shock. In a piglet model of endotoxin (ETX) induced septic shock, we examined possible mechanisms for why eVP may not achieve adequate levels to reverse hypotension. eVP response to a 37% decrease in mean arterial pressure achieved levels of 150 ± 10 pg/mL (n=45) which were not sufficient to raise blood pressure. Plasma VP (pVP) levels achieved with pharmacologically administered vasopressin (VP) at 1, 10, and 100 ng/kg/min revealed that pVP levels of at least 400 pg/mL were needed to reverse hypotension (p<0.05). For piglets given ETX, pituitary levels of VP were measured and found to still contain adequate stores (735 ± 51 ng/pit) although decreased from non‐ETX controls (1297 ± 290 ng/pit) . Next we examined whether eVP could be further released by other stimuli in the face of endotoxic hypotension. Dopamine was infused in piglets who had the same degree of hypotension as untreated controls and was found to further increase pVP to 203.5 pg/mL ± 34.5, p<0.02. Given these results it appears that the pituitary has the stores and the capacity to release more eVP in septic shock. The mechanism responsible for low levels of pVP therefore seems to be due at least in part to the inability of the pituitary to adequately release the hormone in response to endotoxin‐induced hypotension.