Renal interstitial adenosine is increased in angiotensin II-induced hypertensive rats

Abstract

Since marked renal vasoconstriction is observed in angiotensin II (ANG II)-mediated hypertensive rats, we studied the possible interaction between ANG II and adenosine in this model. ANG II was infused into male Wistar rats through osmotic minipumps (435 ng·kg−1·min−1) for 14 days. In sham and ANG II groups, renal tissue and interstitial adenosine were measured; both increased to a similar twofold extent in the ANG II-treated rats (31.40 ± 4 vs. 62.0 ± 8.4 nM, sham vs. ANG 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-cyclopentyl-1,3-dipropylxanthine, 10 μg·kg−1·min−1). 5′-Nucleotidase and adenosine deaminase (ADA) activities were measured in the cytosolic and membrane fractions. Only the membrane ADA activity decreased from 1,202 ± 80 to 900 ± 50 mU/mg protein in the ANG II-treated rats ( P< 0.05), as well as in their protein and mRNA expression. Despite the adenosine elevation, A1and A2breceptor protein did not change; in contrast, downregulation was observed in A2areceptor and upregulation in A3receptor. A similar pattern was found in the cortex and in the medulla; mRNA significantly decreased only in the A3receptor in both segments. These results suggest that the elevation of renal tissue and interstitial adenosine contributes to the renal vasoconstriction observed in the ANG II-induced hypertension and that it is mediated by a decrease in the activity and expression of ADA, increased production of adenosine, and an induced imbalance in adenosine receptors.