Since marked renal vasoconstriction is observed in angiotensin II-mediated hypertensive rats, we studied the possible interaction between angiotensin II and adenosine in this model. Angiotensin II was infused into male Wistar rats through osmotic minipumps (435ng/kg/min) for 14 days. In Sham and Angiotensin II groups, renal tissue and interstitial adenosine were measured; both increased to a similar two-fold extent in the angiotensin II-treated rats (31.40±4 nM Sham vs. 62.0±8.4 nM Angiotensin II, interstitial adenosine p<0.001) the latter decreased by 47 % with the specific blockade of 5'-nucleotidase. Glomerular hemodynamics demonstrated marked renal vasoconstriction in the angiotensin-treated group, which was reverted by an adenosine A1 receptor antagonist (8-cylopentyl-1,3-dipropylxanthine, 10 µg/k/min). 5'-nucleotidase and adenosine deaminase activity was measured in the cytosolic and membrane fractions. Only the membrane adenosine deaminase activity decreased from 1202±80 to 900±50 mU/mg protein in the Angiotensin II-treated rats (p<0.05), as well as in their protein and mRNA expression. In spite of the adenosine elevation, A1 and A2b receptor protein did not change; in contrast, down-regulation was observed in A2a receptor and up-regulation in A3 receptor; a similar pattern was found in the cortex and in the medulla; mRNA significantly decreased only in the A3 receptor in both segments. These results suggest that the elevation of renal tissue and interstitial adenosine contributes to the renal vasoconstriction observed in the angiotensin II-induced hypertension, and that it is mediated by a decrease in the activity and expression of adenosine deaminase, increased production of adenosine, and an induced imbalance in adenosine receptors.