Differential sympathetic response to lesion-induced chronic kidney disease in rabbits

Sata, Yusuke; Burke, Sandra L.; Watson, Anna; Jha, Jay C.; Gueguen, Cindy; Eikelis, Nina; Lim, Kieran F.; Jackson, Kristy L.; Lambert, Gavin W.; Jandeleit‐Dahm, Karin; Denton, Kate M.; Esler, Murray; Schlaich, Markus P.; Head, Geoffrey A.

doi:10.1016/j.kint.2020.03.039

Cited by 3 publications

(13 citation statements)

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“…15,16 Measurement of total norepinephrine spillover was included to determine whether overall sympathetic activity was affected. We also determined whether a longer period of CKD would alter the renal inflammation, fibrosis, and oxidative stress, which we previously reported 11 and whether any changes we observed were dependent on afferent or efferent renal nerves. As in the previous studies, we examined the effect of TRD and ARD on cardiac and sympathetic baroreflexes as well as responses to hypoxia and aversive stress to gauge the extent of changes to the more dynamic responsivity of the sympathetic nervous system.…”

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confidence: 83%

“…The first operation involved lesioning the surface of the left or sham lesioning in which the kidney was exposed but not lesioned (see Data Supplement). 11 After 2 weeks, rabbits underwent a right nephrectomy where the right kidney was removed via a retroperitoneal incision (CKD groups) or sham nephrectomy, which involved an incision, but the kidney was not disturbed (sham groups). For TRD of the right kidney in shams, all visible nerves were transected and the adventitia of the artery stripped and painted with 10% phenol (sham+TRD).…”

Section: Methodsmentioning

confidence: 99%

“…18 The central ear artery was catheterized as above, and RSNA was filtered outside 50 to 1000 Hz, rectified, and integrated (20 ms). 11,13 Resting parameters were recorded for 1 hour. Responses to airjet (60 L/minute for 10 minutes) and hypoxia (10% O 2 +3% CO 2 in N 2 for 20 minutes 19 ) were measured in the second and fourth week (Figure S1).…”

Section: Methodsmentioning

confidence: 99%

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Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

et al. 2021

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There is increasing evidence that renal denervation is effective in alleviating hypertension associated with elevation of renal sympathetic nerve activity (RSNA) in chronic kidney disease (CKD), but whether this is due to reduction in renal afferent signaling is unclear. We determined the cardiovascular and sympathetic effects of total renal denervation or afferent renal denervation (topical capsaicin) on CKD induced by glomerular layer lesioning of the left kidney and right nephrectomy in conscious rabbits. CKD increased blood pressure by 18±2 mmHg and plasma creatinine by 40% over 2 to 4 weeks (both P <0.001), while RSNA (43%) and total norepinephrine spillover (28%) were elevated in CKD compared with sham (both P =0.04). After total or afferent renal denervation blood pressure, RSNA and norepinephrine spillover were similar or lower than non-CKD (sham) rabbits. While plasma creatinine in CKD rabbits was not affected by total renal denervation, deafferented rabbits had lower levels ( P =0.017). The greater hypotensive response to pentolinium in CKD was also normalized after total or afferent denervation. Heart rate and RSNA baroreflex gain were similar in all groups. The RSNA response to airjet stress was greater in CKD compared with sham but not after total or afferent renal denervation. By contrast, the sympathetic response to hypoxia was similar in sham and CKD intact or deafferented groups but elevated in total denervated CKD animals. We conclude that the elevated sympathetic activity and blood pressure in this model of CKD is predominantly driven by renal afferents.

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confidence: 83%

Section: Methodsmentioning

confidence: 99%

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Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

et al. 2021

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“…Some might argue that the greater SNA in CKD might be a renal-specific response or due to a generalized stimulation of SNS activity. A study performed recently via electro-lesioning 5/6th of the cortex (glomeruli layer) of one kidney on New Zealand rabbits ( Sata et al, 2020 ) compared renal sympathetic activity and NE spillover to those of sham control. Interestingly, their results suggested that nerve overactivity and global SNS activity originate from the kidneys, because circulating NE measurements were not the driver of increased BP in this model ( Sata et al, 2020 ).…”

Section: Pathogenesis Of Hypertension In Chronic Kidney Diseasementioning

confidence: 99%

“…A study performed recently via electro-lesioning 5/6th of the cortex (glomeruli layer) of one kidney on New Zealand rabbits ( Sata et al, 2020 ) compared renal sympathetic activity and NE spillover to those of sham control. Interestingly, their results suggested that nerve overactivity and global SNS activity originate from the kidneys, because circulating NE measurements were not the driver of increased BP in this model ( Sata et al, 2020 ). These aforementioned results suggest that perhaps renal denervation may present a more effective treatment approach than the use of sympatholytic drugs in the context of systemic hypertension in CKD.…”

Section: Pathogenesis Of Hypertension In Chronic Kidney Diseasementioning

confidence: 99%

Hypertension in chronic kidney disease: What lies behind the scene

Ameer

2022

Front. Pharmacol.

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Hypertension is a frequent condition encountered during kidney disease development and a leading cause in its progression. Hallmark factors contributing to hypertension constitute a complexity of events that progress chronic kidney disease (CKD) into end-stage renal disease (ESRD). Multiple crosstalk mechanisms are involved in sustaining the inevitable high blood pressure (BP) state in CKD, and these play an important role in the pathogenesis of increased cardiovascular (CV) events associated with CKD. The present review discusses relevant contributory mechanisms underpinning the promotion of hypertension and their consequent eventuation to renal damage and CV disease. In particular, salt and volume expansion, sympathetic nervous system (SNS) hyperactivity, upregulated renin–angiotensin–aldosterone system (RAAS), oxidative stress, vascular remodeling, endothelial dysfunction, and a range of mediators and signaling molecules which are thought to play a role in this concert of events are emphasized. As the control of high BP via therapeutic interventions can represent the key strategy to not only reduce BP but also the CV burden in kidney disease, evidence for major strategic pathways that can alleviate the progression of hypertensive kidney disease are highlighted. This review provides a particular focus on the impact of RAAS antagonists, renal nerve denervation, baroreflex stimulation, and other modalities affecting BP in the context of CKD, to provide interesting perspectives on the management of hypertensive nephropathy and associated CV comorbidities.

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Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease

et al. 2020

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Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis. After 3-week CKD, blood pressure was 13±2 mm Hg higher than at baseline ( P <0.001), and compared with sham control rabbits, renal sympathetic nerve activity was 1.2±0.5 normalized units greater ( P =0.01). The depressor response to ganglion blockade was also +8.0±3 mm Hg greater, but total norepinephrine spillover was 8.7±3.7 ng/min lower (both P <0.05). RDN CKD rabbits only increased blood pressure by 8.0±1.5 mm Hg. Renal sympathetic activity, the response to ganglion blockade and diuresis were similar to sham denervated rabbits (non-CKD). CKD rabbits had intact renal sympathetic baroreflex gain and range, as well as normal sympathetic responses to airjet stress. However, hypoxia-induced sympathoexcitation was reduced by −9±0.4 normalized units. RDN did not alter the sympathetic response to hypoxia or airjet stress. CKD increased oxidative stress markers Nox5 and MCP-1 (monocyte chemoattractant protein-1) in the kidney, but RDN had no effect on these measures. Thus, RDN is an effective treatment for hypertension in this model of CKD without further impairing renal function or altering the normal sympathetic reflex responses to various environmental stimuli.

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Differential sympathetic response to lesion-induced chronic kidney disease in rabbits

Cited by 3 publications

References 54 publications

Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

Hypertension in chronic kidney disease: What lies behind the scene

Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease

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