Abstract
Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure.Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys.Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation.Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation.
Highlights
Chronic kidney disease (CKD) is often initiated as a consequence of structural deterioration within the renal vascular and tubular structures and impairs renal function which eventually impinges on cardiovascular homeostasis (Khawaja and Wilcox, 2011; Sobotka et al, 2011)
By contrast, following cisplatin administration in the Renal failure (RF) rats, FENa and noradrenaline excretion were some three-fold higher on day 8, urine flow rate remained at the same level
Cisplatin given to the renally denervated rats (RF DNX) had no effect on FENa, noradrenaline excretion or urine flow rate at day 8 as the values were not significantly different from those recorded on day 1
Summary
Chronic kidney disease (CKD) is often initiated as a consequence of structural deterioration within the renal vascular and tubular structures and impairs renal function which eventually impinges on cardiovascular homeostasis (Khawaja and Wilcox, 2011; Sobotka et al, 2011). Patients with end stage renal disease have elevated muscle sympathetic nerve activity (MSNA) and that removal of the diseased kidneys, at or following transplantation of a functional kidney, decreased blood pressure, peripheral resistance, and the bursting rate in MSNA to normal values (Converse et al, 1992; Hausberg et al, 2002). It has been reported that ablation of the renal nerves in patients with CKD, whilst not impacting on renal function itself delayed the deterioration in kidney function and resulted in a chronic reduction in blood pressure (Ott et al, 2015)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
