NATRIURETIC EFFECT OF AN ADENOSINE-1 RECEPTOR ANTAGONIST IN CIRRHOTIC-PATIENTS WITH ASCITES

Background & Aims: The sodium and water retention and renal vasoconstr iction exhibited by patients with cirrhotic ascites are similar to the changes observed by stimulation of renal adenosine 1 receptors. The a im of this study was to investigate the effects of FK352 (an adenosine 1 antagonist) on renal and systemic hemodynamics and renal function i n cirrhotic patients with ascites. Methods: p-Aminohippuric acid and i nulin clearance, urine flow rate, sodium and potassium excretion, and free water clearance were measured for 2 hours before and after FK352 administration. Cardiac output, systemic vascular resistance, plasma a ngiotensin II level, plasma renin activity, and noradrenaline, adrenal ine, and adenosine 3',5'-cyclic monophosphate (cAMP) levels were also measured before and after FK352. Results: Urine sodium excretion and u rine flow rate increased after FK352 by a mean of 199.9% +/- 43.0% (P < 0.001) and 51.2% +/- 17.5% (P < 0.02), respectively. Plasma cAMP and angiotensin II levels and plasma renin activity also increased by 10. 8% +/- 3.2% (P < 0.01), 36.9% +/- 11.3% (P < 0.01), and 247.9% +/- 82. 6% (P < 0.02), respectively. No change was detected in any other param eter. Conclusions: The isokaliuretic improvement in natriuresis and di uresis suggests a role for adenosine 1 antagonism in the treatment of the renal abnormalities found in advanced cirrhosis.