Vasopressin Regulation and Potassium Homeostasis Following Recovery from Severe Blood loss in a Conscious Rat Model of Hemorrhagic Shock
Authors: Uyehara Catherine , Hernandez Claudia A , Murata Lee‐Ann M , Lee Debby , Wong Lauren N , Blythe Jauchia 
Published: November 2023

In an anesthetized, mechanically ventilated pig model, we have found that non‐survival in the first minutes after severe hemorrhage is associated with a rapid elevation in plasma potassium (K) and a blunted endogenous vasopressin(VP) response in non‐survivors compared to survivors. We have also shown that exogenously administered VP during hemorrhage resuscitation causes a dramatic increase in urine flow and can increase the fractional excretion of K compared to other pressor agents. Thus, early survival of acute rapid blood loss in severe hemorrhage may depend on the ability of VP to regulate renal normalization of circulating plasma K levels. It is unknown what may prevent an adequate endogenous VP response that would allow renal K excretion to be maintained in the face of low urine output during hemorrhage‐induced hypotensive shock. Aside from responding only to hypotension and hyperkalemia, other factors of electrolyte or acid‐base balance may also affect VP regulation of K balance. Thus, in this study, we tested the hypothesis that VP regulation may be affected by other fluid and electrolyte changes that occur in different stages of hemorrhage induced‐shock, resuscitation, and recovery. Hence, we examined circulating VP and K levels in the face of changes in acid‐base homeostasis in a conscious rat model where animals are able to adjust spontaneously breathing in response to hemorrhage. Renal K handling and regulation of VP in rats (n=35) were compared before, during, and after hemorrhage(2 ml shed blood/100 g body weight), one hour after hemorrhage resuscitation with normal saline, and 3 and 7 days after hemorrhage. Hematocrit (Hct) was 36±1%, 27±1%,25±1%,29±1%, 37±1 % at baseline, hemorrhage, resuscitation, 3 days and7 days post‐hemorrhage, respectively. Plasma K increased (3.61±0.07 to 4.27±0.13mEq/L, p<0.05) and urine K levels increased (86±8 to 190±9 mEq/L, p<0.05)during hemorrhage. An increased renal trans‐tubular K gradient during hemorrhage and resuscitation (10.7 ± 0.5 to 16.4 ± 0.9, p<0.05) occurred co‐incident with a 7‐fold the increase in plasma VP with hemorrhage, and returned to baseline levels with resuscitation. Multiple regression analysis of indices of blood gases and electrolytes during post‐hemorrhage recovery when Hct had not yet returned to normal, revealed that VP levels were correlated with plasma K, blood pH and oxygen saturation. Indicative of the stimulation of VP release and renal action during hemorrhage, VP pituitary content, renal V2 receptor mRNA expression and pituitary V1b receptor mRNA expression 7days after recovery correlated with vasopressin responses at different timepoints after hemorrhage. Results support an important role for VP in protecting against hyperkalemia in hemorrhagic shock, with VP responsiveness being influenced by changes in blood gases and acid‐base regulation.

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