Absence of effect of diazoxide on sodium and water handling in the isolated perfused rat kidney.

The effect of the thiazide derivative diazoxide on water and sodium handling of the isolated perfused rat kidney was studied. In kidneys of normotensive rats no influence on diuresis, glomerular filtration rate or sodium and potassium excretion rates could be detected whereas hydrochlorothiazide showed the anticipated effects. The diuretic effect of the latter compound was not inhibited nor potentiated by pretreatment with diazoxide. In kidneys of hypertensive rats, studied at different ages: 10, 20, 30, and 45 weeks respectively, no acute effects of diazoxide on tubular function were found either. Diazoxide and hydrochlorothiazide both resulted into a small drop of renal perfusion pressure indicating that renal vascular resistance was lowered. The results suggest that the water and sodium retention frequently observed in patients treated with diazoxide are not caused by a direct effect of the drug on tubular function but are mediated by its peripheral and/or intrarenal vascular effects.