The role of antidiuretic hormone in the impaired water excretion of isolated glucocorticoid deficiency was investigated in the thyroxin-replaced, anterior hypophysectomized rat. Hypophysectomized rats demonstrated marked impairment in the excretion of an oral water load (32 ± 4% vs.94 ± 4%), plasma hypoosmolality (281 ± 2 vs. 289 ± 2 mOsm/kg), and hyponatremia (129 ± 1 vs. 140 ± 1 mEq/liter) compared to controls (all P < 0.001). These defects were associated with increased levels of plasma arginine vasopressin (3.05 ± 0.45 vs. 1.38 ± 0.11 pg/ml; P < 0.001). Following physiologic corticosterone replacement in hypophysectomized rats, the percentage of the water load excreted, free water clearance, plasma sodium, plasma osmolality, and circulating levels of plasma arginine vasopressin were all restored to control values. This correction of water diuresis occurred in the absence of changes in GFR or solute excretion. The defect in water excretion and the elevation of plasma arginine vasopressin could not be corrected by chronic extracellular volume expansion in the absence of glucocorticoid replacement. It is concluded that (a) increased secretion of vasopressin plays an important role in the impaired water diuresis of isolated glucocorticoid deficiency; (b) physiologic corticosterone replacement corrects both the impaired water excretion and the increased secretion of vasopressin associated with glucocorticoid deficiency; and (c) a volume-independent nonosmotic stimulus to vasopressin secretion may be activated by the chronic absence of glucocorticoid hormones.
ASJC Scopus subject areas