Arginine vasopressin metabolism in dogs. II. Modeling and system analysis.

System modeling and analysis methods were applied to interpret data regarding arginine vasopressin (AVP) metabolism in dogs. Based on this analysis a new nonlinear 3-pool model of AVP distribution and disposal was proposed and quantified; the model pools included the plasma, a receptor pool, and an extravascular nonreceptor pool. The receptor pool mediated a portion of the rapid flux of hormone between the plasma and the extravascular pool. Mathematical analysis indicated that the plasma AVP impulse response (bolus) data would be insufficient to uniquely estimate all the model constants, but additional plasma impulse data using 125I-labeled AVP, which does not bind to physiologic hormone receptors, would allow unique model quantification. Other required measurements were the urinary excretion of intact hormone, and plasma AVP degradation. The model was successfully fitted to the data from 10 dogs. The results suggest that, in the normal dogs studied, plasma contained 25% of the total AVP, 19% was bound to receptors, and the remaining 56% was in the extravascular pool. Eighty percent of the flux of AVP from the vascular compartment was mediated by the receptor pool; 98% of AVP degradation occurred in the extravascular pool; and urine excretion and plasma degradation made up the remainder.