Renal angiotensin II AT2receptors promote natriuresis in streptozotocin-induced diabetic rats

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Abstract
Angiotensin II AT2receptors have been implicated to play a role in the regulation of renal/cardiovascular functions under pathological conditions. The present study is designed to investigate the function of the AT2receptors on renal sodium excretion and AT2receptor expression in the cortical membranes of streptozotocin (STZ)-induced diabetic rats. The STZ treatment led to a significant weight loss, hyperglycemia, and decrease in plasma insulin levels compared with control rats. STZ-induced diabetic rats had significantly elevated basal urine flow, urinary sodium excretion rate (UNaV), urinary fractional sodium excretion, and urinary cGMP compared with control rats. Infusion of PD-123319, an AT2receptor antagonist, caused a significant decrease in UNaV (μmol/min) in STZ-induced diabetic rats (1 ± 0.09 vs. 0.45 ± 0.1) but not in control rats (0.35 ± 0.05 vs. 0.4 ± 0.07). The decrease in UNaV was associated with a significant decrease in urinary cGMP levels (pmol/min) in STZ-induced diabetic rats (21 ± 2 vs. 10 ± 0.8) but not in control rats (11.75 ± 3 vs. 12.6 ± 2). The infusion of PD-123319 did not alter glomerular filtration rate (STZ: 0.3 ± 0.02 vs. 0.25 ± 0.03; control: 1.4 ± 0.05 vs. 1.5 ± 0.09 ml/min) or mean arterial pressure (STZ: 82 ± 3 vs. 79 ± 3.5; control: 90 ± 4 vs. 89 ± 4 mmHg), suggesting a tubular effect of the drug. Western blot analysis using an AT2receptor antibody revealed a significantly enhanced expression of the AT2receptor protein (∼45 kDa) in brush-border (∼50-fold) and basolateral membranes (∼80-fold) of STZ-induced diabetic compared with control rats. In conclusion, our data suggest that the tubular AT2receptors in diabetic rats are profoundly enhanced and possibly via a cGMP pathway promote sodium excretion in this model of diabetes.