Natriuretic effect of an adenosine-1 receptor antagonist in cirrhotic patients with ascites.
OBJECTIVE
The sodium and water retention and renal vasoconstriction exhibited by patients with cirrhotic ascites are similar to the changes observed by stimulation of renal adenosine 1 receptors. The aim of this study was to investigate the effects of FK352 (an adenosine 1 antagonist) on renal and systemic hemodynamics and renal function in cirrhotic patients with ascites.


METHODS
p-Aminohippuric acid and inulin 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 angiotensin II level, plasma renin activity, and noradrenaline, adrenaline, and adenosine 3', 5'-cyclic monophosphate (cAMP) levels were also measured before and after FK352.


RESULTS
Urine sodium excretion and urine 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 parameter.


CONCLUSIONS
The isokaliuretic improvement in natriuresis and diuresis suggests a role for adenosine 1 antagonism in the treatment of the renal abnormalities found in advanced cirrhosis.
Department of Medicine, Royal Infirmary of Edinburgh, Edinburgh, Scotland.
A J
AJ
Stanley
E H
EH
Forrest
K
K
Dabos
I A
IA
Bouchier
P C
PC
Hayes
D001201:Ascites / Q000209:etiology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006728:Hormones / Q000097:blood; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
C114384:FK 352; D006728:Hormones; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines