Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

Stocker, Sean D.; Muntzel, Martin S.

doi:10.1152/ajpheart.00173.2013

Cited by 46 publications

(39 citation statements)

References 39 publications

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“…Rats have a similar urinary system to humans and rat renal nerves have been visualized by several research groups (Stocker and Muntzel 2013;Miki et al 2002). Non-survival, anesthetized experiments were performed on 24 male 290-550 g Long-Evans and Sprague-Dawley rats (Charles Rivers Laboratories, Wilmington, MA, USA).…”

Section: Animals and Housingmentioning

confidence: 99%

“…Fat and connective tissue surrounding the kidney were separated using cotton-tipped applicators to further expose the kidney and renal artery. A bipolar nerve cuff electrode (1.00 mm inner-diameter, 100 μm platinum contacts, Microprobes for Life Science, Gaithersburg, MD, USA) was placed around the renal artery, encircling renal nerves that run along the artery (Stocker and Muntzel 2013;Miki et al 2002). Care was taken to not damage the renal nerve branches and to not occlude blood flow in the renal artery.…”

Section: Experimental Preparationmentioning

confidence: 99%

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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: Animals and Housingmentioning

confidence: 99%

Section: Experimental Preparationmentioning

confidence: 99%

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

et al. 2018

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“…With the use of a left flank incision, a left renal and splanchnic sympathetic nerve bundle was isolated from surrounding tissue (13,21,42), mounted on a stainless steel wire electrode (0.127-mm OD; A-M Systems), and covered with a silicon-based impression material (Light Body; Coltene) to insulate the recording from body fluids. The recorded signal was directed to an AC amplifier (P511; Grass Technologies) equipped with half-amplitude filters (band pass: 100-1,000 Hz) and a 60-Hz notch filter.…”

Section: Animalsmentioning

confidence: 99%

Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats

Huber

Basu

Cecchettini

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats. Am J Physiol Heart Circ Physiol 309: H880 -H887, 2015. First published June 26, 2015 doi:10.1152/ajpheart.00095.2015.-Previous studies have indicated that hyperactivity of brain prorenin receptors (PRR) is implicated in neurogenic hypertension. However, the role of brain PRR in regulating arterial blood pressure (ABP) is not well understood. Here, we test the hypothesis that PRR activation in the hypothalamic paraventricular nucleus (PVN) contributes to increased sympathetic nerve activity (SNA). In anaesthetized adult Sprague-Dawley (SD) rats, bilateral PVN microinjection of human prorenin (2 pmol/side) significantly increased splanchnic SNA (SSNA; 71 Ϯ 15%, n ϭ 7). Preinjection of either prorenin handle region peptide, the PRR binding blocker (PRRB), or tiron (2 nmol/side), the scavenger of reactive oxygen species (ROS), significantly attenuated the increase in SSNA (PRRB: 32 Ϯ 5% vs. control, n ϭ 6; tiron: 8 Ϯ 10% vs. control, n ϭ 5; P Ͻ 0.05) evoked by prorenin injection. We further investigated the effects of PRR activation on ROS production as well as downstream gene expression using cultured hypothalamus neurons from newborn SD rats. Incubation of brain neurons with human prorenin (100 nM) dramatically enhanced ROS production and induced a time-dependent increase in mRNA levels of inducible nitric oxide synthase (iNOS), NAPDH oxidase 2 subunit cybb, and FOS-like antigen 1 (fosl1), a marker for neuronal activation and a component of transcription factor activator protein-1 (AP-1). The maximum mRNA increase in these genes occurred 6 h following incubation (iNOS: 201-fold; cybb: 2 -fold; Ffosl1: 11-fold). The increases in iNOS and cybb mRNA were not attenuated by the AT 1 receptor antagonist losartan but abolished by the AP-1 blocker curcumin. Our results suggest that PVN PRR activation induces sympathoexcitation possibly through stimulation of an ANG II-independent, ROS-AP-1-iNOS signaling pathway. paraventricular nucleus; (pro)renin receptor; reactive oxygen species; sympathetic nerve activity NEW & NOTEWORTHY To our best knowledge, this study is the first to investigate PVN PRR-mediated ANG II-independent signaling transduction on the control of sympathetic outflow and blood pressure. Our results suggest that PVN PRR-induced sympathoexcitation is possibly mediated by ROS-AP-1-iNOS signal transduction pathways.ACCUMULATING EVIDENCE INDICATES that alteration of central (pro)renin receptor (PRR) is involved in the development of cardiovascular diseases including neurogenic hypertension (32,46). The importance of the brain PRR in cardiovascular control is further strengthened by the observation that increased PRR expression in brain cardiovascular control areas altered body fluid homeostasis (38) and genetic knockdown of the PRR induced long-term depressor effects in hypertensive animals (21,22,38). However, the detailed mechanism underlying the role of brain PRR on blood pressure regulati...

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“…A left flank incision was used to view and isolate a left renal nerve and a postganglionic splanchnic sympathetic nerve from the surrounding tissue (54). Nerve bundles were mounted on separate stainless steel wire electrodes (0.127-mm outer diameter, A-M Systems) and covered with silicon-based impression material (Coltene, Light Body).…”

Section: Methodsmentioning

confidence: 99%

Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus

Larson

Gui

Huber

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered PVN SK channel activity, which may contribute to sympathoexcitation in vivo. In anesthetized rats with normal salt (NS) intake, bilateral PVN microinjection of apamin (12.5 pmol/50 nl each), the SK channel blocker, remarkably elevated splanchnic sympathetic nerve activity (SSNA), renal sympathetic nerve activity (RSNA), and mean arterial pressure (MAP). In contrast, rats with ANG II-salt HTN demonstrated significantly attenuated SSNA, RSNA, and MAP (P < 0.05) responses to PVN-injected apamin compared with NS control rats. Next, we sought to examine the individual contributions of HS and subcutaneous infusion of ANG II on PVN SK channel function. SSNA, RSNA, and MAP responses to PVN-injected apamin in rats with HS alone were significantly attenuated compared with NS-fed rats. In contrast, sympathetic nerve activity responses to PVN-injected apamin in ANG II-treated rats were slightly attenuated with SSNA, demonstrating no statistical difference compared with NS-fed rats, whereas MAP responses to PVN-injected apamin were similar to NS-fed rats. Finally, Western blot analysis showed no statistical difference in SK1-SK3 expression in the PVN between NS and ANG II-salt HTN. We conclude that reduced SK channel function in the PVN is involved in the sympathoexcitation associated with ANG II-salt HTN. Dietary HS may play a dominant role in reducing SK channel function, thus contributing to sympathoexcitation in ANG II-salt HTN.

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Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

Cited by 46 publications

References 39 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

Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats

Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus

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