Effects of intravenous diazoxide and chlorpropamide on renal function in man

The effects of 300 mg. of intravenous diazoxide and 1,000 mg. of intravenous chlorpropamide administered alone and in combination have been studied on specific renal functions in patients with pituitary diabetes insipidus and in a representative patient with essential hypertension during maximal sustained water diuresis as well as in hydropenia during osmotic diuresis produced by the infusion of hypertonic saline. During water diuresis in response to diazoxide within the first 10 to 20 minute urine flow, osmolal clearance and free water clearance increased. This transitory diuretic and natriuretic phase was followed by a marked antidiuresis and antinatriuresis. During water diuresis in the first hour of the study parallel with the decrease in renal plasma flow and glomerular filtration rate a marked reduction in urine flow and sodium excretion occurred. In the second hour antidiuresis and antinatriuresis continued but glomerular filtration rate and renal plasma flow began to approach the initial level. A close correlation was found between the reductions of osmolal and free water clearances both in absolute values and in values expressed in the percentage of GFR, suggesting increased sodium reabsorption in the proximal tubules. During osmotic diuresis diazoxide produced a marked antidiuresis and antinatriuresis apparently of both glomerular and proximal tubular origin, during the whole two hour study, with the exception of the slightly increased urine flow and osmolal clearance per nephron in the first 20 minutes. In patients with diabetes insipidus during the diazoxide induced “proximal type” antidiuresis, there was a parallel decrease in osmolal and free water clearances, whereas during the chlorpropamide induced vasopressin-like “distal type” antidiuresis free water clearance fell 70 per cent without any change in osmolal clearance. Only in the hypertensive patient in response to diazoxide the free water excretion was turned into free water reabsorption, demonstrating that mobilization of ADH may be also involved (as a third mechanism) in the diazoxide induced antidiuresis.