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Renal sympathetic nervous system hyperactivity in early streptozotocin‐induced diabetic kidney disease
Author(s) -
Salman Ibrahim M.,
Ameer Omar Z.,
Sattar Munavvar A.,
Abdullah Nor A.,
Yam Mun F.,
Abdullah Ghassan Z.,
Abdulkarim Muthanna F.,
Khan Md. Abdul Hye,
Johns Edward J.
Publication year - 2011
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.21007
Subject(s) - medicine , endocrinology , renal function , denervation , streptozotocin , kidney , renal blood flow , sympathetic nervous system , diabetes mellitus , hemodynamics , blood pressure
Aim We assessed the role of renal sympathetic nervous system in the deterioration of renal hemodynamic and excretory functions in rats with streptozotocin (STZ)‐induced diabetic kidney disease (DKD). Methods Male Sprague–Dawley (SD) rats were induced with diabetes mellitus (DM) using STZ (55 mg/kg, i.p.). The acute studies were conducted on denervated anesthetized rats 7 days after STZ administration. Two sets of experiments were performed: clearance experiments in which six 20‐min urine and plasma collections were carried out to measure kidney function parameters, and hemodynamic experiments in which the renal nerves were electrically stimulated and responses in renal vascular resistance (RVR) and renal blood flow (RBF) were recorded. Results Renal denervation in STZ‐induced diabetic rats produced higher fractional excretion of sodium (FE Na ) but lower plasma sodium (P Na ), glomerular filtration rate (GFR), and plasma creatinine (P Cr ) (all P < 0.05 vs. innervated diabetic rats). In innervated diabetic rats, renal nerve stimulation (RNS) caused significant attenuation in the renal vasoconstrictor responses (all P < 0.05 vs. innervated control). Renal denervation in diabetic rats significantly blunted these responses (all P < 0.05 vs. innervated diabetic rats); however, they were significantly higher (all P < 0.05) while compared to denervated control counterparts. Conclusions The data demonstrate an early role for the renal sympathetic innervation in the pathogenesis of DKD. If the kidney is prevented from renal sympathetic nerve action renal functional parameters are markedly improved. The data further suggest an early enhancement in renal sensitivity to intrarenal norepinephrine (NE) upon the removal of renal sympathetic tone in STZ‐induced diabetic rats. Neurourol. Urodynam. 30:438–446, 2011. © 2011 Wiley‐Liss, Inc.