The antidiuretic action of hydrochlorothiazide in the hydrated rat

In patients suffering from nephrogenic diabetes insipidus, who are resistant to the action of vasopressin, it is now well established that the normally diuretic compounds derived from thiazide act as antidiuretic agents. It is also agreed that this action is dependent on the maintenance of a negative sodium balance, but there is no generally accepted explanation of the mechanism responsible for these effects. Cutler, Kleeman, Dowling & Maxwell (1960), finding a 30% reduction in filtration rate following chlorothiazide administration in four such patients, concluded that its action was 'probably due to altered body sodium and renal haemodynamics'; but Earley & Orloff (1962), who measured inulin clearance in three patients, found a fall (13-15 %) in only two out of six estimations when hydrochlorothiazide was given. Since the rat has been shown to react like man, in the sense that the diuretic action of chlorothiazide is transformed into an antidiuretic action when diabetes insipidus is induced by bilateral hypothalamic electrolytic lesions (Kennedy & Crawford, 1961; Crawford, Frost, Welsh & Terry, 1962), this species has been used for further investigation of the problem.