The effects of adenosine on water and sodium excretion

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 268; no. 2; pp. 826 - 835
• Main Author: YAGIL, Y
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.02.1994
• Subjects: Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine-5'-(N-ethylcarboxamide); Animals; Biological and medical sciences; Body Water - metabolism; Diuresis - drug effects; Infusions, Intra-Arterial; Infusions, Intravenous; Kidney - drug effects; Kidney - metabolism; Male; Medical sciences; Natriuresis - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Sodium - metabolism; Urinary system; Xanthines - pharmacology; Diuresis; Adenosine; Purine nucleoside; Renal function; Rat; Intrarenal administration; Rodentia; Natriuria; Kidney; Vertebrata; Mammalia; Urinary system; Animal
• ISSN: 0022-3565; 1521-0103

The effects of adenosine on glomerular filtration rate and renal blood flow are well documented, but its effects on water and sodium excretion are less well established. Previous studies in the rat have shown that i.v. and intra-aortic administration of adenosine decrease water and sodium excretion. The validity of these findings was challenged recently when it was found that intrarenal administration of adenosine in the rat induced marked diuresis and natriuresis. The aim of the current study was to investigate further the effects of intrarenal administration of adenosine on renal excretory function in the rat. Intrarenal infusion of 2 to 15 micrograms/min of adenosine, although having no effect on systemic arterial pressure, induced a 4-fold increase in water and sodium excretion. Intravenous infusion of adenosine at equivalent doses in the same species and under similar experimental conditions resulted in a 1-fold increase in water excretion, and only a transient increase in sodium excretion, whereas intraaortic adenosine had no effect on either variable. During infusion of adenosine by all three routes, there was a significant decline in glomerular filtration rate, but no change in renal plasma flow. The diuretic and natriuretic effects of adenosine during intrarenal infusion were of a similar order of magnitude in animals maintained for 3 weeks on no sodium, normal sodium or high sodium diet, and did not correlate with plasma renin activity. Simultaneous infusion of 10(-7) M 9-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist, markedly inhibited the diuretic and natriuretic effects of intrarenal adenosine. Intrarenal infusion of N6-cyclohexyladenosine, an adenosine A1 receptor agonist, but not of N' ethylcarboxamidoadenosine, a potent A2 receptor agonist, significantly increased water and sodium excretion. These findings suggest that, in the rat, the diuretic and natriuretic effects of adenosine are 1) fully expressed only during intrarenal administration, 2) absent during intra-aortic administration, 3) not related to prior sodium intake or sodium balance, 4) mediated by the adenosine A1 receptor and 5) dissociated from its effects on glomerular filtration and renal plasma flow.