NATRIURETIC AND HYPOTENSIVE EFFECT OF ADENOSINE-1 BLOCKADE IN ESSENTIAL-HYPERTENSION

We studied the effects of a single dose (100 mg orally) and repeated a dministration (100 mg o.d. for 7 days) of FK453, a novel adenosine-1 r eceptor antagonist, on renal sodium handling and blood pressure in eig ht patients with essential hypertension. Within 60 minutes after admin istration of FK453, sodium excretion increased threefold. This occurre d in the absence of a change in renal hemodynamics, assessed from inul in and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by incr eased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery ter m and a decrease in the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not o ccur until about 3 hours after ingestion, that is, when the natriuresi s was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied by some net sodium retention. Blood pressure on the seventh day before FK453 treatment w as not different from blood pressure before administration of the firs t dose of FK453. Again an acute natriuretic response followed, althoug h less than after the first dose. Changes in intrarenal sodium handlin g parameters, blood pressure, and heart rate were similar to those see n after the first dose. The natriuretic and hypotensive effects of FK4 53 indicate that adenosine-1 receptor activity plays a role in the reg ulation of blood pressure and renal sodium handling in patients with e ssential hypertension. Although these findings are not necessarily spe cific for this condition, it seems worthwhile to evaluate whether aden osine-1 antagonism can be used as a mode to treat hypertension.