The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to intracerebroventricular (ICV) infusion of clonidine in diabetic rats. Diabetes was induced in male Sprague-Dawley rats by 65 mg/kg i.p. injection of streptozocin, and control rats were injected with vehicle 2 wk before the experiment. Blood glucose levels were significantly elevated in the diabetic group (26.3 ± 1.3 mM) compared with the control group (8.4 ± 1.6 mM). Before and during ICV infusion of clonidine (2 μg · kg−1 · min−1 for 45 min), urine flow and sodium excretion were measured from intact and denervated kidneys in anesthetized diabetic and control rats. The ICV infusion of clonidine significantly increased urine flow in both innervated and denervated kidneys from control rats but not from diabetic rats. There was a significant increase in sodium excretion during ICV infusion of clonidine from innervated kidneys of control rats, and denervation abolished this effect. In diabetic rats, clonidine failed to promote natriuresis from intact kidneys, and similar to control rats, did not promote natriuresis in denervated kidneys. This study demonstrates that 1) the diuretic response to the ICV infusion of clonidine is blunted in diabetic rats, and 2) a natriuretic response to the ICV infusion of clonidine is blunted in innervated kidneys of diabetic rats.

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