Role of vasopressin in the impaired water excretion of glucocorticoid deficiency

Abstract

The mechanism whereby glucocorticoid deficiency impairs renal water excretion was studied in the conscious mineralocorticoid-replaced, adrenalectomized rat. Control animals received physiologic replacement with prednisolone, and experimental animals were deprived of glucocorticoid hormone for either 1 or 14 days. The control animals excreted 95 +/- 1.9% of an acute water load (30 ml/kg) in 3 hours, a value significantly higher than the volume excreted by animals deprived fo glucocorticoid hormone for 1 day (70.0 +/- 3.6%, P less than 0.01) and 14 days (40.0 +/- 3.9%, P less than 0.01). Following the acute water load, plasma vasopressin levels, as measured by radioimmunoassay, was 1.08 pg/ml in the control rats, a value significantly lower than values obtained after the water load in rats deprived of glucocorticoid hormone for 1 day (2.5 +/- 0.2 pg/ml, P less than 0.01) and 14 days (2.4 +/- 0.3 pg/ml, P less than 0.01). To further examine the effect of plasma vasopressin in the impaired water excretion of glucocorticoid deficiency, we performed studied in Brattleboro rats with central diabetes insipidus. In these animals with absence of vasopressin, a defect in water excretion was observed after 14 days, but no 1 day, of glucocorticoid deficiency. In Sprague-Dawley rats, the impaired water excretion after 14 days of glucocorticoid deficiency was associated with a significantly lower cardiac index (209 +/- 14 vs. 291 +/- 11 ml/min/kg, P less than 0.01) and renal blood flow (3.8 +/- 0.3 vs. 5.7 +/- 0.2 ml/min/g, P less than 0.01) than that observed after 1 day of glucocorticoid deficiency. In diabetes insipidus rats, after 14 days of glucocorticoid deficiency, the percentage of an acute water load excreted (121 +/- 7% vs. 158.7 +/- 7.0%, P less than 0.01) was lower than that observed after 1 day of glucocorticoid deficiency. In summary, the present results indicate that glucocorticoid deficiency impairs renal water excretion by both vasopressin-dependent and vasopressin-independent mechanisms. The vasopressin-dependent renal mechanism is associated with a marked decrease in both systemic and renal hemodynamics.

A Case of Isolated ACTH Deficiency Who Developed Autoimmune-Mediated Hypothyroidism and Impaired Water Diuresis during Glucocorticoid Replacement Therapy.

“…Glucocorticoids have been found to act directly on the hypothalamus and tonically inhibit ADH release by magnocellular neurosecretory neurons [22], and plasma ADH has been found to increase in glucocorticoid deficiency [23]. These findings suggest that sustained and nonsuppressive ADH secretion because of the glucocorticoid deficiency may have played a role in the pathogenesis of hyponatremia in the present case; however, that fails to fully explain the impaired water diuresis on the second admission.…”

Severe chronic hiponatremia: rare cause of adrenal insufficiency

“…Pero el mecanismo es distinto al aceptado para la deficiencia de mineralocorticoides, desde el momento que por la deficiencia de glucocorticoides per se no se genera hipovolemia ni balance negativo de sodio. (8) Es conocido el rol de la vasopresina en la generación de hiponatremia euvolémica, debido a insuficiencia suprarrenal o hipotiroidismo (9,10,11,12,13) Parece claro sin embargo, que existen factores independientes de la vasopresina que también están comprometidos en la excreción alterada del agua que cursa con la deficiencia de glucocorticoides. Así, mientras el componente vasopresina-dependiente puede ser observado en ratas adrenalectomizadas privadas de glucocorticoides por 24 horas, el efecto vasopresina independiente de la excreción de agua ocurre luego de 2 semanas de deficiencia de glucocorticoides, en ratas deficientes en vasopresina.…”

Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency

“…In addition, the expression of aquaporin-2 (AQP-2) water channel mRNA and protein in kidney was upregulated in glucocorticoid-deficient rats (12). Hydrocortisone replacement corrected the defect in renal water excretion and normalized plasma AVP levels and kidney AQP-2 mRNA expression in glucocorticoid deficiency (6,7,12).…”

“…Studies performed in isolated glucocorticoid deficiency showed that impaired water excretion occurred in the patients with hypopituitarism and in experimental models of glucocorticoid deficiency (3,(5)(6)(7)(8)(9)(10). Non-suppressible release of arginine vasopressin (AVP) was found despite hypo-osmolality which should suppress AVP release to undetectable levels (3,6,7,11). In addition, the expression of aquaporin-2 (AQP-2) water channel mRNA and protein in kidney was upregulated in glucocorticoid-deficient rats (12).…”

“…There has been an important debate since the 1950s regarding the mechanisms for hyponatremia in adrenal insufficiency, that is, whether water retention or renal deficit of sodium (Na) is more prominent in producing hyponatremia (2 -6). Studies performed in isolated glucocorticoid deficiency showed that impaired water excretion occurred in the patients with hypopituitarism and in experimental models of glucocorticoid deficiency (3,(5)(6)(7)(8)(9)(10). Non-suppressible release of arginine vasopressin (AVP) was found despite hypo-osmolality which should suppress AVP release to undetectable levels (3,6,7,11).…”