INCREASED SENSITIVITY OF THE RENAL VASCULATURE TO ADENOSINE IN STREPTOZOTOCIN-INDUCED DIABETES-MELLITUS RATS

Adenosine (ADO) has been implicated as a pathophysiological factor in contrast media (CM)-induced acute renal failure, which has been encountered more often in patients with diabetes and impaired renal function. Therefore, we studied the renal vascular response to exogenous and endogenous ADO in streptozotocin-induced diabetic rats. We found that exogenous ADO (0.01-100 nmol), injected into the abdominal aorta, decreased renal blood flow (RBF) in a dose-dependent manner. The dose-response curve was shifted to the left by factor 30 in diabetic, compared with nondiabetic rats rats. Renal vascular response to endogenous ADO, assessed by postocclusive reduction of RBF after a 30-s renal artery occlusion, was significantly enhanced (P < 0.001) in diabetic rats (75.6 +/- 3.9%) compared with nondiabetic rats (36.5 +/- 2%). ADO A(1)-receptor blockade with 8-cyclopentyl-1,3-dipropylxanthine attenuated exogenous and endogenous ADO-induced renal vasoconstriction in both groups. We conclude that the ADO Al-receptor signal-transduction chain is altered in diabetic animals and that the enhanced vasoconstrictive action of ADO could be involved in the kidney pathophysiology of diabetes mellitus.