Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure.
OBJECTIVE
There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure.


METHODS
Renal failure was induced using cisplatin (5 mg kg(-1) , i.p.) and the rats used 7 days later. Groups of rats were anaesthetized and prepared for measurement of renal sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal denervation was performed, and renal sympathetic nerve activity and heart rate baroreflex gain curves were generated while the cardiopulmonary receptors were stimulated using an acute saline volume load.


RESULTS
Cisplatin administration reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional excretions fourfold, plasma creatinine and kidney index by 39 and 30% respectively, (all P < 0.05) compared with control rats. In the renal failure rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control animals. Bilateral, but not unilateral, renal denervation restored baroreflex sensitivity to normal values. Volume expansion reduced (P < 0.05) renal sympathetic nerve activity by 34% in control rats, but remained unchanged in the renal failure rats. Unilateral and bilateral renal denervation progressively restored the volume expansion induced renal sympathoinhibition to control values.


CONCLUSIONS
These findings reveal a significant role of the renal sensory innervation in cisplatin-damaged kidneys which blunt the normal baroreflex control of renal sympathetic nerve activity.
Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
S A
SA
Khan
M A
MA
Sattar
H A
HA
Rathore
M H
MH
Abdulla
F
F
Ud Din Ahmad
A
A
Ahmad
S
S
Afzal
N A
NA
Abdullah
E J
EJ
Johns
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D002945:Cisplatin / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000633:toxicity; D004195:Disease Models, Animal; D006339:Heart Rate / Q000502:physiology*; D007668:Kidney / Q000294:innervation* / Q000502:physiology*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D013562:Sympathectomy
D003432:Cross-Linking Reagents; D002945:Cisplatin
baroreceptor reflexes; cisplatin-induced renal failure; renal denervation; renal sympathetic nerve activity