Diazoxide and renal function in man

In 14 patients with hypertension, 4 mg. at diazoxide per kilogram of body weight iniected intravenously caused an 18 per cent reduction in mean blood pressure, 18 per cent reduction in para‐aminohippurate (PAH) clearance, 27 per cent reduction in inulin clearance, and 50 per cent reduction in uric acid clearance. Marked reduction in urinary sodium, potassium, and chloride excretion occurred. Whereas all of these effects were immediate in onset and sustained, free water clearance fell progressively in over half the subiects and became negative in 7 during the second hour after iniection. There was no correlation between antinatriuresis and change in renal hemodynamics, blood pressure, or tree water clearance. In 6 patients with hypertension, 2 mg. of diazoxide per kilogram injected intravenously caused no change in blood pressure or clearances of inulin or PAH. However, uric acid clearance fell 23 per cent, and clear reductions in urinary electrolyte excretion occurred. In 2 subiects, free water clearance fell progressively and became negative 1.5 to 2.5 hours after iniection. On a constant diet, 300 mg. of diazoxide daily by mouth caused weight gain and sodium retention with minimal change in blood pressure or creatinine clearance. This dosage did not alter free water clearance during sustained water diuresis. The acute antihypertensive effect of diazoxide is associated with reduced renal blood flow and glomerular filtration rate (GFR). Antinatriuresis can occur without change in blood pressure or GRF and is probably caused by a direct tubular action of diazoxide. Frequent marked reduction in free water clearance suggests stimulation of pituitary release of antidiuretic hormone. Diazoxide also suppresses tubular uric acid excretion.