Autonomous innervation in renal inflammatory disease—innocent bystander or active modulator?

Ditting, Tilmann; Tiegs, Gisa; Veelken, Roland

doi:10.1007/s00109-009-0498-4

Cited by 20 publications

(19 citation statements)

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“…1,[12][13][14] Our findings are compatible with the possibility that the renal afferent nerve can increase brain oxidative stress, leading to arterial pressure elevation through sympathoexcitation. These findings support other reports showing brain ROS overproduction in the phenol renal injury model of hypertension 27 and the 2-kidney, 1-clip hypertension model.…”

Section: Fujita Et Al Sympathoexcitation Via Brain Ros In Ckd 109supporting

confidence: 84%

“…Although both of them are important in the pathophysiology of hypertension, 11 the renal afferent nerve has been suggested to contribute to sympathetic activation and the resultant hypertension in the diseased kidney. 1,[12][13][14] Afferent renal denervation prevented the development of hypertension in 5/6 nephrectomized rats. 12 Renal injury may activate afferent pathways connecting with brain regions involved in the control of blood pressure.…”

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confidence: 96%

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Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease

et al. 2012

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Abstract-Hypertension is very prevalent in chronic kidney disease and critical for its prognosis. Sympathoexcitation and oxidative stress have been demonstrated to be involved in chronic kidney disease. We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in the salt-sensitive hypertension model, Dahl salt-sensitive rats. Thus, we investigated whether sympathoexcitation by excessive brain oxidative stress could contribute to arterial pressure elevation in salt-induced chronic kidney disease model rats. Young (3-week-old) male Sprague-Dawley rats were randomly assigned to a uninephrectomy or sham operation and then subjected to either a normal salt (0.5%) or high-salt (8.0%) diet for 4 weeks. The young salt-loaded uninephrectomized rats exhibited sympathoexcitation, hypertension, and renal injury, proteinuria and global glomerulosclerosis together with tubulointerstitial damage. Under urethane anesthesia and artificial ventilation, renal sympathetic nerve activity, arterial pressure, and heart rate decreased to a greater degree in the salt-loaded uninephrectomized rats than in the nonsalt-loaded uninephrectomized rats and the salt-loaded or nonsalt-loaded sham-operated rats, when Tempol, a membrane-permeable superoxide dismutase mimetic, was infused acutely into the lateral cerebral ventricle. Oxidative stress in the hypothalamus, measured by lucigenin chemiluminescence, was also significantly greater. Furthermore, in the salt-loaded uninephrectomized rats, antioxidant treatment with chronic intracerebroventricular Tempol decreased sympathetic nerve activity and arterial pressure, which, in turn, led to a decrease in renal damage. Similar effects were elicited by treatment with oral moxonidine, the central sympatholytic agent.

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Section: Fujita Et Al Sympathoexcitation Via Brain Ros In Ckd 109supporting

confidence: 84%

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confidence: 96%

Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease

et al. 2012

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“…6 Furthermore, it is very likely that afferent nerve fibers are able to secrete transmitters, specifically substance P (SP) and calcitonin gene-related peptide (CGRP), as described for other organ systems where these substances are released from afferent peptidergic nerve fibers, which might even be aggravated in inflammation. 7,8 Astonishingly, these peptides may be secreted along the whole surface of the axon 9 and not only at the nerve endings as described very recently for vagal afferent sensory nerve fibers. 10 Afferent and efferent nerve fibers lie in close proximity to each other within the kidney.…”

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confidence: 74%

“…Release of neurogenic SP from peptidergic afferent nerve fibers in inflammation has been described for other organ systems than the kidney. 7,8 …”

Section: Perspectivementioning

confidence: 99%

Tonic Postganglionic Sympathetic Inhibition Induced by Afferent Renal Nerves?

et al. 2012

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Abstract-Other than efferent sympathetic innervation, the kidney has peptidergic afferent fibers expressing TRPV1 receptors and releasing substance P. We tested the hypothesis that stimulation of afferent renal nerve activity with the TRPV1 agonist capsaicin inhibits efferent renal sympathetic nerve activity tonically by a neurokinin 1 receptordependant mechanism. Anesthetized Sprague-Dawley rats were instrumented as follows: (1) arterial and venous catheters for recording of blood pressure and heart rate and drug administration; (2) left-sided renal arterial catheter for selective intrarenal administration of the TRPV1 agonist capsaicin (3.3, 6.6, 10, 33*10 Ϫ7 M; 10 L; after 15, 30, 45, and 60 minutes, respectively) to stimulate afferent renal nerve activity; (3) right-sided bipolar electrode for continuous renal sympathetic nerve recording; and (4) specialized renal pelvic and renal artery catheters to separate pelvic from intrarenal afferent activity. Before and after intrarenal capsaicin application, increasing intravenous doses of the neurokinin 1 receptor blocker RP67580 were given. Intrarenal capsaicin decreased integrated renal sympathetic activity from 65.4Ϯ13.0 mV*s (baseline) to 12.8Ϯ3.2 mV*s (minimum; PϽ0.01). This sustained renal sympathetic inhibition reached its minimum within 70 minutes and was not directly linked to the transient electric afferent response to be expected with intrarenal capsaicin. Suppressed renal sympathetic activity transiently but completely recovered after intravenous administration of the neurokinin 1 blocker (maximum: 120.3Ϯ19.4 mV*s; PϽ0.01). Intrarenal afferent activity could be unequivocally separated from pelvic afferent activity. For the first time we provide direct evidence that afferent intrarenal nerves provide a tonically acting sympathoinhibitory system, which seems to be rather mediated by neurokinin release acting via neurokinin 1 receptor pathways rather than by electric afferent effects on central sympathetic outflow. Key Words: renal nerve Ⅲ afferent Ⅲ efferent Ⅲ TRPV1 Ⅲ NK 1 -receptor Ⅲ tonic inhibition T he kidney has a very complex sympathetic efferent and peptidergic afferent innervation 1 that recently became of increased interest as renal nerve ablation was introduced into the treatment of severely hypertensive patients. 2 However, especially the role of the afferent renal innervation in hypertension is still far from being fully understood. 3 We know that afferent renal nerve traffic is able to suppress the contralateral renal nerve activity by a sympathodepressory renorenal reflex that is altered in hypertension. 4 So far afferent nerve fibers involved in this reflex were said to be mainly projecting from the renal pelvis to the first neuron in the dorsal root ganglion, 5 although afferent nerve fibers are also found intrarenally in close vicinity to efferent sympathetic nerve fibers. 6 Furthermore, it is very likely that afferent nerve fibers are able to secrete transmitters, specifically substance P (SP) and calcitonin gene-related peptide (CGRP), ...

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“…Despite the recognized complexity of renal innervation and its role in blood pressure regulation, its interaction with renal inflammation has so far not been appreciated. Ditting et al report recent findings on the impact of mechanical denervation and pharmacological interference with neurotransmitter release in different animal models of kidney disease [7]. These findings suggest that in particular yet unrecognized peptidergic sensory neurons play an important role, since they can induce local neurogenic inflammation via paracrine effects of their transmitters and also increase sympathetic outflow of the kidneys.…”

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confidence: 99%

Frontiers in the pathogenesis of kidney disease

Eckardt

2009

J Mol Med

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Autonomous innervation in renal inflammatory disease—innocent bystander or active modulator?

Cited by 20 publications

References 40 publications

Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease

Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease

Tonic Postganglionic Sympathetic Inhibition Induced by Afferent Renal Nerves?

Frontiers in the pathogenesis of kidney disease

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