Preferential Renal Sympathetic Hyperactivity in Experimental Diabetes Mellitus

Autonomic, cardiovascular and renal dysfunction has been observed in diabetic patients and animal models of diabetes mellitus (DM), including the streptozotocin‐induced type 1 diabetes model. The aim of this study was to evaluate the effects of the experimental DM on efferent post‐ganglionic sympathetic nerve activity, arterial baroreceptor reflex sensitivity to heart rate (HR), renal (rSNA) and lumbar (lSNA) sympathetic nerves in DM rats. The DM was induced by Streptozotocin (60 mg/kg, ip) 4 weeks before experimental analysis. Male Wistar rats (n=6–8 per group), 8 weeks of age, 230–250 g of body weight were used. The animals were separated into control (CTR) and diabetic (DM) groups. Protocol CEUA/UNIFESP 1787250714. The results were expressed as mean ± SEM and compared with t ‐Student test (p<0.05). DM was confirmed by the reduction in body weight (CTR: 320.1±6.3; DM: 242.1±6.7 g, p<0.05) and significantly increased in blood glucose (CTR: 100.3±3.7; DM: 509.1±14.4 mg/dL, p<0.05) in the DM group. A significant increase in feed intake (CTR: 75.8±3; DM: 158.3±6.4 g/kg), water intake (CTR: 98±4.3; DM: 608±31,3 ml/kg), and urinary flow in the DM rats evaluated for 24h (CTR: 40±3.1; DM: 562±25,1 ml/kg) was found. Sodium urinary excretion (CTR: 5.1±0.5; DM: 17.4±1.2 mmol/kg), potassium (CTR: 16±0.9; DM: 36.4±1 mEq/kg), glucose (CTR: 12±1.4; DM: 2719±192 mg/kg), and albumin urinary excretion (CTR: 82.3±8; DM: 394.3±42.7 mg/kg) were significantly increased in DM group. In addition, sodium (CTR: 123±1.7; DM: 141.4±1.6 mmol/L) and potassium plasma concentration (CTR: 4.4±0.1; DM: 5.2±0.1 mEq/L) were significantly increased in DM rats compared to control group. The creatinine clearance was reduced in the DM rats (CTR: 1.4±0.1; DM: 1±0.1 mL/min). DM reduced heart rate (HR) (CTR: 352.6±013.5; DM: 292.2±11 bpm, p<0.05), but did not change basal values of blood pressure (BP) compared to control group. rSNA was significantly increased (CTR: 85.5±3.1; DM: 133.5±2.5 pps) but lSNA did not change in DM rats. The arterial baroceptor function was significantly decreased to rSNA, (CTR: 1.3±0.1; DM: 0.9±0.1 pps/mmHg), lSNA (CTR: 1.4±0.1, DM: 0.8±0.1 pps/mmHg) and HR control (tachycardic response = CTR: −1.4 ± 0.1; DM: 0.8 ± 0.05 and bradycardic response = CTR: 1.3 ± 0.05; DM: 0.7 ± 0.03 bpm/mmHg, respectively) in the DM group compared to control rats. Taken altogether, the results suggest that autonomic dysfunction, characterized by impaired baroreceptor function, preferential increasein renal sympathetic nerve activity associated with impaired renal function are involved in the development and/or maintenance of experimental DM. Whether the renal sympathoexcitation in DM is a cause or a consequence of renal dysfunction remains to be determined. Support or Funding Information CAPES and FAPESP.