Peer-Reviewed Journal Details
Mandatory Fields
Salman, IM,Ameer, OZ,Sattar, MA,Abdullah, NA,Yam, MF,Abdullah, GZ,Abdulkarim, MF,Khan, MAH,Johns, EJ;
2011
January
Urology
Renal Sympathetic Nervous System Hyperactivity in Early Streptozotocin-Induced Diabetic Kidney Disease
Validated
()
Optional Fields
diabetic kidney disease renal denervation renal nerve stimulation renal sympathetic nerve streptozotocin SPRAGUE-DAWLEY RATS GLOMERULAR HYPERFILTRATION ALPHA(1)-ADRENOCEPTOR SUBTYPES CARDIOVASCULAR-DISEASE EXCRETORY FUNCTIONS HYPERTENSIVE-RATS NEPHROPATHY MELLITUS DENERVATION SUPERSENSITIVITY
30
438
446
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 (FENa) but lower plasma sodium (P-Na), glomerular filtration rate (GFR), and plasma creatinine (PCr) (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. (C) 2011 Wiley-Liss, Inc.
DOI 10.1002/nau.21007
Grant Details