Antidiuretic properties of chlorothiazide in diabetes insipidus dogs

Abstract

Chlorothiazide was found to decrease urine volume and increase urine concentration in diabetes insipidus dogs. There was no change in GFR, RPF, TmPAH, plasma volume, extracellular fluid or total body water. The one consistent altered function was a decrease in “free water” clearance. Diazoxide and mercuhydrin were not antidiuretic. It is believed that the antidiuretic action is dependent on the chlorothiazide-induced saluresis. Although the mechanism of this antidiuresis has not been clearly defined, it seems best explained by postulating a decrease in filtrate reaching the distal nephron (giving a decreased final urine volume) coupled with inhibition of solute reabsorption in the distal tubule (preventing the selective reabsorption of solute in the distal tubule that is normally seen, accounting for the increase in urine concentration). The possible role of the mineralocorticoids in the antidiuretic response to chlorothiazide therapy was investigated in diabetes insipidus and adrenalectomized dogs. Administration of sodium-retaining steroids to diabetes insipidus dogs did not reproduce the urinary changes associated with chlorothiazide therapy. In addition, the antidiuretic response to chlorothiazide was not altered by adrenalectomy or spironolactone administration. Therefore, the presence of the sodium-retaining steroids are not essential for the antidiuretic response of chlorothiazide in diabetes insipidus.