Characterization of renal hemodynamic and structural alterations in rat models of renal impairment: role of renal sympathoexcitation.
BACKGROUND
Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment.


METHODS
Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment.


RESULTS
In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls.


CONCLUSIONS
Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.
Salman
Ibrahim M
IM
Department of Cardiovascular and Renal Physiology and Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia. ibraheem_muhammed@yahoo.com
Ameer
Omar Z
OZ
Sattar
Munavvar A
MA
Abdullah
Nor A
NA
Yam
Mun F
MF
Najim
Hafsa S
HS
Abdulkarim
Muthanna F
MF
Abdullah
Ghassan Z
GZ
Kaur
Gurjeet
G
Khan
Md Abdul Hye
MA
Johns
Edward J
EJ
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002945:Cisplatin; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D006439:Hemodynamics; D007668:Kidney / Q000098:blood supply* / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors; D014655:Vascular Resistance; D014661:Vasoconstriction
D002945:Cisplatin