Renal actions of theophylline and atrial natriuretic peptide in humans: a comparison by means of clearance studies.

The hypothesis that the methylxanthine theophylline and atrial natriuretic peptide (ANP) have similar actions in the kidney was tested. Doses of equal natriuretic potency were administered to seven healthy men during maximal water diuresis. Theophylline (1.2 mg/kg/min) increased sodium excretion to 3-fold, increased glomerular filtration rate and filtration fraction and had no effect on estimated renal plasma flow. Increments were also found in maximal urine flow, distal delivery index and fractional lithium clearance. Diluting segment reabsorption index decreased, and minimal urine osmolality increased. ANP, of which the dose was low (0.01 micrograms/kg/min), had similar effects on sodium excretion, glomerular filtration rate, filtration fraction, minimal urine osmolality and diluting segment reabsorption index, but it decreased estimated renal plasma flow and had no effect on distal delivery and fractional lithium clearance. In a third clearance study ANP was infused after 3 days of treatment with theophylline. The only difference observed was that theophylline prevented the ANP-induced fall in estimated renal plasma flow. Theophylline did not enhance the natriuretic effect of ANP nor its effect to stimulate urinary cyclic guanosine monophosphate. Pretreatment with theophylline had raised plasma renin activity, but the effect of ANP to lower plasma renin activity was not diminished. Our observations agree with the idea that theophylline and ANP act via common mechanisms in the kidney. However, ANP effects are independent of theophylline's action.