Renal nerve stimulation leads to the activation of the Na<sup>+</sup>/H<sup>+</sup>exchanger isoform 3 via angiotensin II type I receptor

Pontes, Roberto Braz; Crajoinas, Renato Oliveira; Nishi, Érika E.; Oliveira‐Sales, Elizabeth Barbosa; Girardi, Adriana C. C.; Campos, Rui; Bergamaschi, Cássia T.

doi:10.1152/ajprenal.00515.2014

Cited by 48 publications

(45 citation statements)

References 61 publications

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“…This associated response may suggest that either UGE or UFR was the primary effect of stimulation, while the other was a secondary response. Previous studies that applied stimulation of renal nerves at low frequencies observed a 25-52% reduction in UFR (Bello-Reuss et al 1976;Pontes et al 2015). Those percentages align with the average reduction of UFR we observed at low frequency stimulation (28% at 2 Hz, 41% at 5 Hz), suggesting that UFR may be the primary response of stimulation at low frequencies.…”

Section: Discussionsupporting

confidence: 89%

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

et al. 2018

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Background: The role of the kidney in glucose homeostasis has gained global interest. Kidneys are innervated by renal nerves, and renal denervation animal models have shown improved glucose regulation. We hypothesized that stimulation of renal nerves at kilohertz frequencies, which can block propagation of action potentials, would increase urine glucose excretion. Conversely, we hypothesized that low frequency stimulation, which has been shown to increase renal nerve activity, would decrease urine glucose excretion. Methods: We performed non-survival experiments on male rats under thiobutabarbital anesthesia. A cuff electrode was placed around the left renal artery, encircling the renal nerves. Ureters were cannulated bilaterally to obtain urine samples from each kidney independently for comparison. Renal nerves were stimulated at kilohertz frequencies (1-50 kHz) or low frequencies (2-5 Hz), with intravenous administration of a glucose bolus shortly into the 25-40-min stimulation period. Urine samples were collected at 5-10-min intervals, and colorimetric assays were used to quantify glucose excretion and concentration between stimulated and non-stimulated kidneys. A KruskalWallis test was performed across all stimulation frequencies (α = 0.05), followed by a post-hoc Wilcoxon rank sum test with Bonferroni correction (α = 0.005). Results: For kilohertz frequency trials, the stimulated kidney yielded a higher average total urine glucose excretion at 33 kHz (+ 24.5%; n = 9) than 1 kHz (− 5.9%; n = 6) and 50 kHz (+ 2.3%; n = 14). In low frequency stimulation trials, 5 Hz stimulation led to a lower average total urine glucose excretion (− 40.4%; n = 6) than 2 Hz (− 27.2%; n = 5). The average total urine glucose excretion between 33 kHz and 5 Hz was statistically significant (p < 0.005). Similar outcomes were observed for urine flow rate, which may suggest an associated response. No trends or statistical significance were observed for urine glucose concentrations. Conclusion: To our knowledge, this is the first study to investigate electrical stimulation of renal nerves to modulate urine glucose excretion. Our experimental results show that stimulation of renal nerves may modulate urine glucose excretion, however, this response may be associated with urine flow rate. Future work is needed to examine the underlying mechanisms and identify approaches for enhancing regulation of glucose excretion.

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Section: Discussionsupporting

confidence: 89%

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

et al. 2018

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“…Another important factor to consider is renal sympathetic nervous system activation secondary to renal injury which prevents retraction of NHE3 out of the microvilli in the face of hypertension and blunts natriuresis. 5, 55, 56 …”

Section: Mediators Of Pressure Natriuresismentioning

confidence: 99%

Maintaining Balance Under Pressure

McDonough

Nguyen

2015

Hypertension

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“…Moreover, these effects were completely blunted by AT 1 receptor blockade prior to low‐frequency RNS (Pontes et al . ).…”

Section: Introductionmentioning

confidence: 97%

“…In addition, we have recently found that low‐frequency RNS significantly increases intrarenal, but not systemic, Ang II (Pontes et al . ). These studies further our understanding of the crosstalk between the renal sympathetic nerve and intrarenal Ang II, which influences sodium and water reabsorption.…”

Section: Introductionmentioning

confidence: 97%

Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption

Pontes

Girardi

Nishi

et al. 2015

Experimental Physiology

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New Findings r What is the topic of this review?The sympathetic control of renal sodium tubular reabsorption is dependent on activation of the intrarenal renin-angiotensin system and activation of the angiotensin II type 1 (AT 1 ) receptor by angiotensin II. r What advances does it highlight?Despite the fact that the interaction between the sympathetic nervous system and angiotensin II regarding salt reabsorption is a well-known classical mechanism for the maintenance of extracellular volume homeostasis, the underlying molecular signalling is not clearly understood. It has been shown recently that renal nerve stimulation increases intrarenal angiotensin II and activates the AT 1 receptor, triggering a signalling cascade that leads to elevations of Na + -H + exchanger isoform 3-mediated tubular transport. In this short review, the crosstalk between intrarenal angiotensin II and renal nerve activity and its effect on sodium reabsorption is addressed.In this review, we address the importance of the interaction between the sympathetic nervous system and intrarenal renin-angiotensin system in modulating renal tubular handling of sodium and water. We have recently shown that increased Na + -H + exchanger isoform 3 (NHE3) activity induced by renal nerve stimulation (RNS) depends on the activation of the angiotensin II type 1 (AT 1 ) receptor by angiotensin II (Ang II). Low-frequency RNS resulted in higher levels of intrarenal angiotensinogen and Ang II independent of changes in blood pressure, the glomerular filtration rate and systemic angiotensinogen. Angiotensin II, via the AT 1 receptor, triggered an intracellular pathway activating NHE3 in the renal cortex, leading to antinatriuresis and antidiuresis. Pharmacological blockade of the AT 1 receptor with losartan prior to RNS abolished both the functional and the molecular responses, suggesting that intrarenal Ang II acting via the AT 1 receptor is a major factor for NHE3-mediated sodium and water reabsorption induced by RNS.

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Renal nerve stimulation leads to the activation of the Na⁺/H⁺exchanger isoform 3 via angiotensin II type I receptor

Cited by 48 publications

References 61 publications

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

Maintaining Balance Under Pressure

Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption

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Renal nerve stimulation leads to the activation of the Na+/H+exchanger isoform 3 via angiotensin II type I receptor

Cited by 48 publications

References 61 publications

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

Electrical stimulation of renal nerves for modulating urine glucose excretion in rats

Maintaining Balance Under Pressure

Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption

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Product

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Renal nerve stimulation leads to the activation of the Na⁺/H⁺exchanger isoform 3 via angiotensin II type I receptor