An experimental model of syndrome of inappropriate antidiuretic hormone secretion in the rat

An experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was developed using continuous subcutaneous infusions of arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (DDAVP) in conscious unrestrained rats drinking 5% dextrose solution. Retention of both ingested water and endogenously generated free water from tissue catabolism was the primary determinant of hyponatremia using either AVP or DDAVP infusions. Natriuresis occurred transiently following water expansion but only slightly further lowered plasma [Na+]. Cessation of antidiuretic infusion resulted in free water excretion with correction of plasma [Na+]. Erythrocyte cell volume was significantly increased in hyponatremic animals and intracellular [K+] and [Na+] both decreased equivalently, consistent with dilution of intracellular fluid by retained water. This model of SIADH differs significantly from those previously described, in that escape from the hydroosmotic effect of AVP and DDAVP does not occur in the absence of high urinary flow rates. The observed results using this model suggest that the retained water in SIADH primarily resides intracellularly following isotonic equilibration of extracellular fluid volume.