Salt and Water Metabolism and Neurohypophyseal Vasopressor Activity in Mice With Hereditary Nephrogenic Diabetes Insipidus

Abstract

Three genotypes of mice, VII Os/+, DI +/+ and DI Os/+, with nephrogenic (vasopressin resistant) diabetes insipidus (DI) are compared to a normal VII +/+ strain with respect to water intake, urine output, urine osmolality, urine sodium and potassium, and the extractable vasopressor (ADH) activity from the neurohypophysis. From the results obtained, it is confirmed that the severely diabetic DI Os/+ mice produce large volumes of dilute, hypotonic urine and have a 2\m=1/2\fold vasopressor increase as compared to normal VII +/+ mice, whereas, the mildly diabetic VII Os/+ and DI +/+ stand in between the DI Os/+ and VII +/+ with intermediate volumes of hypertonic urine and a vasopressor increase of 1\m=1/3\and 1\m=1/2\fold respectively. Further, a parallelism between the severity of diabetes insipidus and increased vasopressor activity is demonstrated in this study.The total excretion of sodium in the urine of VII Os/+ and DI Os/+ is higher than that of the VII +/+ and DI +/+ mice. This natriuresis is associated with Os gene and furthermore, its possible hypothalamic involvement is discussed. The increase of ADH in these hereditary nephrogenic diabetes insipidus mice is a new syndrome and the possible role of other factors involved is discussed.

Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus

“…Using this knockout strategy, mice lacking AQP2 or the V2R appeared to suffer from severe NDI, resulting in perinatal death (173,174). In contrast, mice lacking AQP3, SPA-1, Foxa1, CLC-K1, or all three nitric oxide synthase (NOS) isoforms, or expressing overactive PDE-III, showed milder forms of NDI (12,76,86,93,101,106,111,156). While a role of AQP3 (exit of water from principal cells) ands PDE-III (reduced intracellular cAMP levels) in AVP-induced AQP2-mediated water transport is obvious, this is not so clear for the others.…”