REDUCED RENAL SYMPATHOINHIBITION IN RESPONSE TO ACUTE VOLUME EXPANSION IN DIABETIC RATS

To determine whether the renal sympathetic nerve responses to acute volume expansion (VE) are altered in the diabetic state, we measured the acute VE-induced renal sympathoinhibition in streptozotocin (STZ)-induced diabetic rats. Urine flow, sodium excretion, and integrated renal sympathetic nerve activity were measured before and during an acute graded VE (with isotonic saline) in anesthetized (Inactin; 0.1 g/kg ip) control rats (vehicle; n = 7), diabetic rats (Sprague-Dawley rats injected with STZ 65 mg/kg ip 2 wk before experiment; n = 7), and diabetic rats treated with insulin (2 U/day sc; n = 6). Blood glucose levels were significantly elevated in the diabetic group (370 +/- 8 mg/dl) compared with the control group (104 +/- 3 mg/dl). Acute graded VE with isotonic saline produced a significantly blunted renal sympathoinhibition (50% of control by 10% VE), diuresis (19% of control by 10% VE), and natriuresis (24% of control by 10% VE) in the diabetic rats compared with control rats. Treatment with insulin for 2 wk to restore normoglycemia in diabetic rats (third group; 93 +/- 9 mg/dl) resulted in reversal of the blunted urine flow, sodium excretion, and renal sympathoinhibition in response to acute VE. However, acute (a few hours before VE challenge) reduction of hyperglycemia in the diabetic rats (125 +/- 18 mg/dl) did not correct the blunted renal sympathoinhibition. The second goal of this study was to determine if enalapril treatment (10 mg/day by mouth) for 2 wk corrects the blunted volume reflex in diabetic rats. Enalapril did not correct the blunted renal excretory and renal nerve responses to acute VE in diabetic rats. This study demonstrates that 1) there is a blunted renal sympathoinhibition concomitant with blunted natriuresis and diuresis in response to acute VE in STZ-induced diabetic rats, 2) restoring the glucose levels to normal by chronic insulin treatment in the diabetic rats normalized the renal responses to VE, and 3) 2 wk of enalapril treatment does not correct the blunted renal responses to acute volume expansion in STZ-induced diabetic rats. We conclude that the altered neural component of the volume reflex is in part responsible for the impaired diuretic and natriuretic responses to acute volume expansion in the early stage of diabetes.