THE EFFECTS OF ADENOSINE ON WATER AND SODIUM-EXCRETION

The effects of adenosine on glomerular filtration rate and renal blood flow are well documented, but its effects on water and sodium excreti on are less well established. Previous studies in the rat have shown t hat i.v. and intra-aortic administration of adenosine decrease water a nd sodium excretion. The validity of these findings was challenged rec ently when it was found that intrarenal administration of adenosine in the rat induced marked diuresis and natriuresis. The aim of the curre nt study was to investigate further the effects of intrarenal administ ration of adenosine on renal excretory function in the rat. Intrarenal infusion of 2 to 15 mu g/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 dose s in the same species and under similar experimental conditions result ed in a 1-fold increase in water excretion, and only a transient incre ase in sodium excretion, whereas intraaortic adenosine had no effect o n either variable. During infusion of adenosine by all three routes, t here was a significant decline in glomerular filtration rate, but no c hange in renal plasma flow. The diuretic and natriuretic effects of ad enosine during intrarenal infusion were of a similar order of magnitud e in animals maintained for 3 weeks on no sodium, normal sodium or hig h sodium diet, and did not correlate with plasma renin activity. Simul taneous infusion of 10(-7) M 9-cyclopentyl-1,3-dipropylxanthine, a sel ective adenosine A1 receptor antagonist, markedly inhibited the diuret ic and natriuretic effects of intrarenal adenosine. Intrarenal infusio n of Ne-cyclohexyladenosine, an adenosine A1 receptor agonist, but not of N'ethylcarboxamidoadenosine, a potent A2 receptor agonist, signifi cantly increased water and sodium excretion. These findings suggest th at, in the rat, the diuretic and natriuretic effects of adenosine are 1) fully expressed only during intrarenal administration, 2) absent du ring intra-aortic administration, 3) not related to prior sodium intak e or sodium balance, 4) mediated by the adenosine A1 receptor and 5) d issociated from its effects on glomerular filtration and renal plasma flow.