RENAL RESPONSES TO ACUTE VOLUME EXPANSION AND ATRIAL-NATRIURETIC-FACTOR IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to volume expansion (VE) and atrial natriuretic factor (ANF) in 4-week diabetic rats. Diabetes was induced in two groups of male Sprague Dawley rats using streptozotocin (STZ), while a control group of rats was treated with vehicle alone, four weeks prior to the experiment. One group of diabetic rats was treated daily with insulin for the four weeks prior to the experiment. Before, during and after VE (1.2 ml/min for 15 min), urine flow and sodium excretion were measured from innervated and denervated kidneys in the three groups of anesthetized rats. Then the renal response to infusion of ANF (0.25-mu-g/kg/min for 15 min) were observed in these rats. During VE, urine flow and sodium excretion from innervated kidneys, but not from denervated kidneys, were significantly lower in diabetic rats than those in control rats. Urine flow and sodium excretion from innervated as well as denervated kidneys of the diabetic rats failed to increase compared to the control rats in response to ANF. Correcting the diabetic condition with insulin (third group) rectified the blood glucose levels and the blunted responses to either VE or ANF. At the initial level, glomerular filtration rate (GFR) was not significantly different among the three groups. During VE and ANF infusion, changes in GFR was not parallel to changes in excretory parameters, therefore the hemodynamic change may not be the main reason for the blunted renal responses in diabetic rats. This study demonstrates that: (1) the volume reflex is blunted in the 4-week diabetic rats, which is in part due to the presence of tonic renal nerve activity, (2) renal responses to ANF are blunted in the 4-week diabetic rats, and (3) insulin treatment in diabetic rats normalizes the altered renal responses to either acute volume expansion or ANF.