Function of Renal Nerves in Kidney Physiology and Pathophysiology

2021 ◽  
Vol 83 (1) ◽  
pp. 429-450
Author(s):  
John W. Osborn ◽  
Roman Tyshynsky ◽  
Lucy Vulchanova
Keyword(s):  
Current Knowledge ◽  
Sensory Nerves ◽  
Renal Nerves ◽  
Sodium Reabsorption ◽  
Renal Nerve ◽  
Kidney Physiology ◽  
Afferent Nerves ◽  
Renal Nerve Ablation ◽  
The Brain ◽  
Renal Sympathetic

Renal sympathetic (efferent) nerves play an important role in the regulation of renal function, including glomerular filtration, sodium reabsorption, and renin release. The kidney is also innervated by sensory (afferent) nerves that relay information to the brain to modulate sympathetic outflow. Hypertension and other cardiometabolic diseases are linked to overactivity of renal sympathetic and sensory nerves, but our mechanistic understanding of these relationships is limited. Clinical trials of catheter-based renal nerve ablation to treat hypertension have yielded promising results. Therefore, a greater understanding of how renal nerves control the kidney under physiological and pathophysiological conditions is needed. In this review, we provide an overview of the current knowledge of the anatomy of efferent and afferent renal nerves and their functions in normal and pathophysiological conditions. We also suggest further avenues of research for development of novel therapies targeting the renal nerves.

scholarly journals What we need to know about renal nerve ablation for treatment of hypertension and other states of sympathetic overactivity

2016 ◽  
Vol 311 (6) ◽  
pp. F1267-F1270 ◽  
Author(s):  
Markus P. Schlaich
Keyword(s):  
Blood Pressure ◽  
Renal Disease ◽  
Pressure Control ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Renal Nerve Ablation ◽  
Key Players ◽  
Treatment Of Hypertension ◽  
Recent Developments ◽  
Renal Sympathetic

Renal nerves are key players in the regulation of kidney function and blood pressure control. Targeting the neurogenic mechanisms underlying hypertension and cardiac and renal disease has been attempted by means of surgical and pharmacologic approaches and most recently by catheter-based interventions aimed at disrupting renal sympathetic nerve traffic. The recent developments in the area and the relevant questions that need to be addressed to advance the field further are briefly reviewed in this article.

Lack of effect of chronic renal denervation on altered sodium reabsorption during increased ureteral pressure

1980 ◽  
Vol 58 (5) ◽  
pp. 477-483 ◽  
Author(s):  
D. R. Wilson ◽  
M. Cusimano ◽  
U. Honrath
Keyword(s):  
Isotonic Saline ◽  
Urine Osmolality ◽  
Tubular Reabsorption ◽  
Renal Nerves ◽  
Sodium Reabsorption ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Water Excretion ◽  
Renal Nerve Activity

The role of the renal nerves in the altered sodium reabsorption which occurs during increased ureteral pressure was studied using clearance techniques in anaesthetized rats undergoing diuresis induced by isotonic saline infusion. In rats with a sham denervated kidney, an ipsilateral increase in ureteral pressure to 20 cm H2O resulted in a marked and significant decrease in sodium and water excretion, increased fractional sodium reabsorption, and increased urine osmolality with no significant change in glomerular filtration rate. A similar significant ipsilateral increase in tubular reabsorption of sodium occurred in rats with chronically denervated kidneys during increased ureteral pressure. The changes in tubular reabsorption were rapidly reversible after return of ureteral pressure to normal. These experiments indicate that enhanced tubular reabsorption of sodium during an ipsilateral increase in ureteral pressure is not mediated by increased renal nerve activity. During the antinatriuresis of increased ureteral pressure there was a decrease in the fractional reabsorption of sodium from the opposite normal kidney. The role of the renal nerves in this compensatory change in function in the opposite kidney was studied in two further groups of animals. The renal response to a contralateral increase in ureteral pressure was similar in denervated and sham-denervated kidneys. The results indicate that altered renal nerve activity, through ipsilateral or contralateral renorenal reflexes, is not responsible for the changes in tubular reabsorption of sodium which occur during increased ureteral pressure induced by partial ureteral obstruction.

Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fernanda R Marins ◽  
Aline C Oliveira ◽  
Fatimunnisa Qadri ◽  
Natalia Alenina ◽  
Michael Bader ◽  
...  
Keyword(s):  
Brain Region ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Endogenous Ligand ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Equimolar Dose ◽  
The Brain ◽  
Renal Sympathetic ◽  
Made In

In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to Ang-(1-7) in the brain.

scholarly journals Role of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat

1998 ◽  
Vol 275 (1) ◽  
pp. R194-R202 ◽  
Author(s):  
Chunlong Huang ◽  
Edward J. Johns
Keyword(s):  
Sodium Excretion ◽  
Renal Perfusion ◽  
Urine Flow ◽  
Renal Nerves ◽  
Ang Ii ◽  
Renal Nerve ◽  
Somatosensory Stimulation ◽  
Two Stages ◽  
The Brain

This study examined the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of ANG II was blocked peripherally or selectively within the brain. Activation of skin somatosensory receptors caused a transient reversible 10–15% increase in blood pressure, and while renal perfusion pressure was regulated at control levels, there was a transient fall in urine flow and sodium excretion even though both renal blood flow and glomerular filtration rate were unchanged. These reflexly induced excretory responses were abolished when the renal nerves were sectioned. Administration of the ANG II AT1-receptor antagonist, losartan, either intravenously at 3 or 10 mg/kg or locally into the lateral cerebroventricles at 15 μg plus 7.5 μg/h, had no effect on capsaicin-induced vasopressor responses but blocked the reductions in urine flow and sodium excretion. These findings are consistent with ANG II being involved in at least two stages in the reflex, one centrally and one at the periphery.

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of α1- and α2-adrenoceptors on renal sensory nerve fibers

2007 ◽  
Vol 293 (4) ◽  
pp. R1561-R1572 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Jan Mulder ◽  
Tomas Hökfelt
Keyword(s):  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Renal Sympathetic

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating α-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the α1- and α2-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49°C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 ± 900 and 4,870 ± 670%·s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 ± 210%·s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 ± 1 to 16 ± 1 pg/min, and PGE2 release, from 77 ± 11 to 161 ± 23 pg/min, suggesting a role for PGE2 in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE2. PGE2 enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating α1- and α2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE2.

Impaired neurogenic control of renal vasculature in renal hypertensive rats

1980 ◽  
Vol 238 (6) ◽  
pp. H770-H775 ◽  
Author(s):  
G. D. Fink ◽  
M. J. Brody
Keyword(s):  
Nerve Stimulation ◽  
Sympathetic Innervation ◽  
Renal Hypertension ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Renal Vasculature ◽  
Renal Nerve ◽  
Renal Nerve Stimulation ◽  
Renal Vascular ◽  
Renal Sympathetic

Renal hypertension is accompanied by alterations in the renal sympathetic innervation involving reduced catecholamine content and histofluorescence. Because the renal nerves are a potentially important factor in the pathogenesis of renal hypertension, the functional significance of renal catecholamine depletion was evaluated. In rats with either one-kidney or two-kidney Grollman hypertension, renal vascular responses to renal nerve stimulation and intraarterial administration of vasoactive hormones were assessed in vivo at various times following renal compression. In the wrapped kidney of one-kidney hypertensive rats, vasoconstrictor responses to renal nerve stimulation were consistently reduced, compared to responses in uninephrectomized control rats, whereas responses to intra-arterial norepinephrine were slightly greater in kidneys from hypertensive animals. In the untouched kidney of rats with two-kidney renal hypertension, vasoconstrictor responses to nerve stimulation were also substantially reduced, although those to norepinephrine were only slightly altered. It was concluded that catecholamine depletion in the kidneys of renal hypertensive animals reflects a diminished capacity of renal sympathetic nerve impulses to produce vasoconstriction. Reduced neurogenic renal vascular resistance may serve to attenuate the rise in blood pressure in renal hypertension.

Role of Renal Nerves in Edema Formation

Physiology ◽  
1994 ◽  
Vol 9 (4) ◽  
pp. 183-188 ◽  
Author(s):  
GF DiBona
Keyword(s):  
Sympathetic Nerve Activity ◽  
Renal Nerves ◽  
Sodium Reabsorption ◽  
Nerve Activity ◽  
Edema Formation ◽  
Renal Sympathetic Nerve Activity ◽  
Important Regulator ◽  
Renal Tubular ◽  
Renal Sympathetic

Once viewed as physiologically insignificant by no less an authority than Homer Smith, the renal nerves have emerged as a physiologically important regulator of renal tubular sodium reabsorption. Increased renal sympathetic nerve activity contributes significantly to the renal sodium retention in edema-forming states.

Basal norepinephrine overflow into the renal vein: effect of renal nerve stimulation

1980 ◽  
Vol 239 (4) ◽  
pp. F371-F377 ◽  
Author(s):  
Juan A. Oliver ◽  
John Pinto ◽  
Robert R. Sciacca ◽  
Paul J. Cannon
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Nerve Stimulation ◽  
Renal Vein ◽  
Renal Nerves ◽  
Plasma Norepinephrine ◽  
Renal Nerve ◽  
Sympathetic Nervous ◽  
Renal Nerve Stimulation ◽  
Renal Sympathetic

In order to determine whether the fraction of norepinephrine released from the renal nerves that escapes into the circulation can be used an an index of renal sympathetic nervous activity, arterial and renal vein plasma norepinephrine concentrations were measured by a radioenzymatic technique along with renal blood flow in anesthetized dogs under control conditions and during electrical renal nerve stimulation. In 25 animais studied under conditions of normal sodium balance, plasma norepinephrine in the renal vein, 198 ± 26 pg/ml, was significantly higher than in arterial blood, 102 ± 10 pg/ml (P < 0.001). In five dogs, electrical stimulation of the renal nerves (12 V, 3 ms) at frequencies of 0.5, 2,6, 12, and 18 Hz for 1 min was associated with increased norepinephrine concentration in renal venous plasma and an increase in the calculated renal norepinephrine overflow. There was a significant linear relationship between the frequency of stimulation and norepinephrine overflow into the renal vein in each animal, but there was also a significant interanimal variation in the slope of this relationship (P <0.01). Electrical stimulation at a frequency of 2 Hz significantly decreased renal blood flow (-24 ± 7 ml/min, P < 0.01). The maximal effect was achieved at 6 Hz (-66 ± 11 ml/min). The data indicate that there is a base-line overflow of norepinephrine into the renal venous blood of the dog that increases with increasing frequency of electrical nerve stimulation. They suggest that measurements of norepinephrine overflow into the renal vein may be used to assess the activity of the renal sympathetic nervous system. renal blood flow; catecholamines; renin; dog Submitted on January 10, 1980 Accepted on April 29, 1980

Altered responsiveness of the kidney to activation of the renal nerves in fat-fed rabbits

2009 ◽  
Vol 296 (6) ◽  
pp. R1889-R1896 ◽  
Author(s):  
Sylvia Michaels ◽  
Gabriela A. Eppel ◽  
Sandra L. Burke ◽  
Geoffrey A. Head ◽  
James Armitage ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Neural Control ◽  
Control Diet ◽  
Plasma Renin ◽  
Sympathetic Nerves ◽  
Urine Flow ◽  
Renal Nerves ◽  
Renal Nerve ◽  
And Control ◽  
Renal Sympathetic

We tested whether mild adiposity alters responsiveness of the kidney to activation of the renal sympathetic nerves. After rabbits were fed a high-fat or control diet for 9 wk, responses to reflex activation of renal sympathetic nerve activity (RSNA) with hypoxia and electrical stimulation of the renal nerves (RNS) were examined under pentobarbital anesthesia. Fat pad mass and body weight were, respectively, 74% and 6% greater in fat-fed rabbits than controls. RNS produced frequency-dependent reductions in renal blood flow, cortical and medullary perfusion, glomerular filtration rate, urine flow, and sodium excretion and increased renal plasma renin activity (PRA) overflow. Responses of sodium excretion and medullary perfusion were significantly enhanced by fat feeding. For example, 1 Hz RNS reduced sodium excretion by 79 ± 4% in fat-fed rabbits and 46 ± 13% in controls. RNS (2 Hz) reduced medullary perfusion by 38 ± 11% in fat-fed rabbits and 9 ± 4% in controls. Hypoxia doubled RSNA, increased renal PRA overflow and medullary perfusion, and reduced urine flow and sodium excretion, without significantly altering mean arterial pressure (MAP) or cortical perfusion. These effects were indistinguishable in fat-fed and control rabbits. Neither MAP nor PRA were significantly greater in conscious fat-fed than control rabbits. These observations suggest that mild excess adiposity can augment the antinatriuretic response to renal nerve activation by RNS, possibly through altered neural control of medullary perfusion. Thus, sodium retention in obesity might be driven not only by increased RSNA, but also by increased responsiveness of the kidney to RSNA.

The renal afferent nerves in the pathogenesis of hypertension

1987 ◽  
Vol 65 (8) ◽  
pp. 1548-1558 ◽  
Author(s):  
Suzanne Oparil ◽  
Wanida Sripairojthikoon ◽  
J. Michael Wyss
Keyword(s):  
Renal Denervation ◽  
Genetic Model ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Experimental Models ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Afferent Nerves ◽  
Hypertensive Rat

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate – salt (DOCA–NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.

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