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  • 1
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    Online Resource
    EMPAGLIFLOZIN IMPROVES IMPAIRED SENSITIVITY OF AFFERENT NEURONS WITH RENAL AXONS
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of Hypertension Vol. 41, No. Suppl 3 ( 2023-06), p. e75-
    Details
    In: Journal of Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. Suppl 3 ( 2023-06), p. e75-
    Type of Medium: Online Resource
    ISSN: 0263-6352 , 1473-5598
    URL: Article
    DOI: 10.1097/01.hjh.0000939476.31391.6e
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2017684-3
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  • 2
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    Neurogenic substance P—influences on action potential production in afferent neurons of the kidney?
    Springer Science and Business Media LLC ; 2021
    In:  Pflügers Archiv - European Journal of Physiology Vol. 473, No. 4 ( 2021-04), p. 633-646
    Details
    In: Pflügers Archiv - European Journal of Physiology, Springer Science and Business Media LLC, Vol. 473, No. 4 ( 2021-04), p. 633-646
    Abstract: We recently showed that a substance P (SP)–dependent sympatho-inhibitory mechanism via afferent renal nerves is impaired in mesangioproliferative nephritis. Therefore, we tested the hypothesis that SP released from renal afferents inhibits the action potential (AP) production in their dorsal root ganglion (DRG) neurons. Cultured DRG neurons (Th11-L2) were investigated in current clamp mode to assess AP generation during both TRPV1 stimulation by protons (pH 6) and current injections with and without exposure to SP (0.5 µmol) or CGRP (0.5 µmol). Neurons were classified as tonic (sustained AP generation) or phasic (≤ 4 APs) upon current injection; voltage clamp experiments were performed for the investigation of TRPV1-mediated inward currents due to proton stimulation. Superfusion of renal neurons with protons and SP increased the number of action potentials in tonic neurons (9.6 ± 5 APs/10 s vs. 16.9 ± 6.1 APs/10 s, P   〈  0.05, mean ± SD, n  = 7), while current injections with SP decreased it (15.2 ± 6 APs/600 ms vs. 10.2 ± 8 APs/600 ms, P   〈  0.05, mean ± SD, n  = 29). Addition of SP significantly reduced acid-induced TRPV1-mediated currents in renal tonic neurons (− 518 ± 743 pA due to pH 6 superfusion vs. − 82 ± 50 pA due to pH 6 with SP superfusion). In conclusion, SP increased action potential production via a TRPV1-dependent mechanism in acid-sensitive renal neurons. On the other hand, current injection in the presence of SP led to decreased action potential production. Thus, the peptide SP modulates signaling pathways in renal neurons in an unexpected manner leading to both stimulation and inhibition of renal neuronal activity in different (e.g., acidic) environmental contexts.
    Type of Medium: Online Resource
    ISSN: 0031-6768 , 1432-2013
    URL: Article
    DOI: 10.1007/s00424-021-02552-z
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1463014-X
    SSG: 12
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  • 3
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    Online Resource
    Responsiveness of afferent renal nerve units in renovascular hypertension in rats
    Springer Science and Business Media LLC ; 2021
    In:  Pflügers Archiv - European Journal of Physiology Vol. 473, No. 10 ( 2021-10), p. 1617-1629
    Details
    In: Pflügers Archiv - European Journal of Physiology, Springer Science and Business Media LLC, Vol. 473, No. 10 ( 2021-10), p. 1617-1629
    Abstract: Previous data suggest that renal afferent nerve activity is increased in hypertension exerting sympathoexcitatory effects. Hence, we wanted to test the hypothesis that in renovascular hypertension, the activity of dorsal root ganglion (DRG) neurons with afferent projections from the kidneys is augmented depending on the degree of intrarenal inflammation. For comparison, a nonhypertensive model of mesangioproliferative nephritis was investigated. Renovascular hypertension (2-kidney, 1-clip [2K1C]) was induced by unilateral clipping of the left renal artery and mesangioproliferative glomerulonephritis (anti-Thy1.1) by IV injection of a 1.75-mg/kg BW OX-7 antibody. Neuronal labeling (dicarbocyanine dye [DiI] ) in all rats allowed identification of renal afferent dorsal root ganglion (DRG) neurons. A current clamp was used to characterize neurons as tonic (sustained action potential [AP] firing) or phasic (1–4 AP) upon stimulation by current injection. All kidneys were investigated using standard morphological techniques. DRG neurons exhibited less often tonic response if in vivo axonal input from clipped kidneys was received (30.4% vs. 61.2% control, p   〈  0.05). However, if the nerves to the left clipped kidneys were cut 7 days prior to investigation, the number of tonic renal neurons completely recovered to well above control levels. Interestingly, electrophysiological properties of neurons that had in vivo axons from the right non-clipped kidneys were not distinguishable from controls. Renal DRG neurons from nephritic rats also showed less often tonic activity upon current injection (43.4% vs. 64.8% control, p   〈  0.05). Putative sympathoexcitatory and impaired sympathoinhibitory renal afferent nerve fibers probably contribute to increased sympathetic activity in 2K1C hypertension.
    Type of Medium: Online Resource
    ISSN: 0031-6768 , 1432-2013
    URL: Article
    DOI: 10.1007/s00424-021-02591-6
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1463014-X
    SSG: 12
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  • 4
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    Abstract P338: High Sodium Intake - Effects On Afferent Renal Nerve Activity
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hypertension Vol. 79, No. Suppl_1 ( 2022-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
    Abstract: Previous work of ours suggests that the sensitivity of renal afferent neurons is decreased under pathological conditions. Here we tested the hypothesis that pathologically decreased sensitivity of renal afferent neurons due to high salt diet is normalized after renal denervation. 6 male Sprague Dawley (SD) rats were put on high salt diet (HS; 8% NaCl) for 10 days. In another group of 18 rats on high salt diet (HS) left kidneys were denervated (DNX) 7 days prior to examination. 17 rats on standard diet with and without DNX were used as controls. Dorsal root ganglion neurons with renal afferents were investigated in primary neuronal cell culture using current clamp mode to assess action potential generation during current injection. Neurons were characterized as tonic highly active ( 〉 5 action potentials, AP) and phasic less active neurons (≤ 5 AP upon stimulation)In renal neurons from rats on HS the relation of tonic to phasic neurons shifted towards less active phasic units (62% tonic neurons in control vs. 42% on HS, p 〈 0.05, z-test). Denervation (DNX) of the left kidney in rats on high salt diet (HS-DNX) led to a recovery of afferent renal DRG neurons remaining vital after denervation. They regained their electrophysiological property of mainly tonic firing (42% tonic neurons in HS vs. 71% HS-DNX, p 〈 0.05, z-test).In rats on high salt diet the proportion of highly active tonic neurons with renal afferents decreased at the expense of less active phasic neurons. This HS effect could be abolished by DNX.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.79.suppl_1.P338
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 5
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    Online Resource
    Tissue sodium content correlates with hypertrophic vascular remodeling in type 2 diabetes
    Elsevier BV ; 2021
    In:  Journal of Diabetes and its Complications Vol. 35, No. 12 ( 2021-12), p. 108055-
    Details
    In: Journal of Diabetes and its Complications, Elsevier BV, Vol. 35, No. 12 ( 2021-12), p. 108055-
    Type of Medium: Online Resource
    ISSN: 1056-8727
    URL: Article
    DOI: 10.1016/j.jdiacomp.2021.108055
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2006763-X
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  • 6
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    Modification of Dialysate Na+ Concentration but not Ultrafiltration or Dialysis Treatment Time Affects Tissue Na+ Deposition in Patients on Hemodialysis
    Elsevier BV ; 2024
    In:  Kidney International Reports Vol. 9, No. 5 ( 2024-05), p. 1310-1320
    Details
    In: Kidney International Reports, Elsevier BV, Vol. 9, No. 5 ( 2024-05), p. 1310-1320
    Type of Medium: Online Resource
    ISSN: 2468-0249
    URL: Article
    DOI: 10.1016/j.ekir.2024.02.002
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2887223-X
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  • 7
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    Afferent renal innervation in anti-Thy1.1 nephritis in rats
    American Physiological Society ; 2020
    In:  American Journal of Physiology-Renal Physiology Vol. 319, No. 5 ( 2020-11-01), p. F822-F832
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 319, No. 5 ( 2020-11-01), p. F822-F832
    Abstract: Afferent renal nerves exhibit a dual function controlling central sympathetic outflow via afferent electrical activity and influencing intrarenal immunological processes by releasing peptides such as calcitonin gene-related peptide (CGRP). We tested the hypothesis that increased afferent and efferent renal nerve activity occur with augmented release of CGRP in anti-Thy1.1 nephritis, in which enhanced CGRP release exacerbates inflammation. Nephritis was induced in Sprague-Dawley rats by intravenous injection of OX-7 antibody (1.75 mg/kg), and animals were investigated neurophysiologically, electrophysiologically, and pathomorphologically 6 days later. Nephritic rats exhibited proteinuria (169.3 ± 10.2 mg/24 h) with increased efferent renal nerve activity (14.7 ± 0.9 bursts/s vs. control 11.5 ± 0.9 bursts/s, n = 11, P 〈 0.05). However, afferent renal nerve activity (in spikes/s) decreased in nephritis (8.0 ± 1.8 Hz vs. control 27.4 ± 4.1 Hz, n = 11, P 〈 0.05). In patch-clamp recordings, neurons with renal afferents from nephritic rats showed a lower frequency of high activity following electrical stimulation (43.4% vs. 66.4% in controls, P 〈 0.05). In vitro assays showed that renal tissue from nephritic rats exhibited increased CGRP release via spontaneous (14 ± 3 pg/mL vs. 6.8 ± 2.8 pg/ml in controls, n = 7, P 〈 0.05) and stimulated mechanisms. In nephritic animals, marked infiltration of macrophages in the interstitium (26 ± 4 cells/mm 2 ) and glomeruli (3.7 ± 0.6 cells/glomerular cross-section) occurred. Pretreatment with the CGRP receptor antagonist CGRP 8–37 reduced proteinuria, infiltration, and proliferation. In nephritic rats, it can be speculated that afferent renal nerves lose their ability to properly control efferent sympathetic nerve activity while influencing renal inflammation through increased CGRP release.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00063.2020
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2020
    detail.hit.zdb_id: 1477287-5
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  • 8
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    Afferent neurons of the kidney with impaired firing pattern in inflammation – role of sodium currents?
    Springer Science and Business Media LLC ; 2023
    In:  Pflügers Archiv - European Journal of Physiology
    Details
    In: Pflügers Archiv - European Journal of Physiology, Springer Science and Business Media LLC
    Abstract: Peripheral neurons with renal afferents exhibit a predominantly tonic firing pattern of higher frequency that is reduced to low frequencies (phasic firing pattern) in renal inflammation. We wanted to test the hypothesis that the reduction in firing activity during inflammation is due to high-activity tonic neurons switching from higher to low frequencies depending on altered sodium currents. We identified and cultivated afferent sensory neurons with renal projections from the dorsal root ganglia (Th11-L2). Cultivated neurons were incubated with the chemokine CXCL1 (1,5 nmol/ml) for 12 h. We characterized neurons as “tonic,” i.e., sustained action potential (AP) firing, or “phasic,” i.e.,  〈  5 APs upon stimulation in the current clamp. Their membrane currents were investigated in a voltage clamp. Data analyzed: renal vs. non-renal and tonic vs. phasic neurons. Renal afferent neurons exposed to CXCL1 showed a decrease in tonic firing pattern (CXCL1: 35,6% vs. control: 57%, P   〈  0.05). Na + and K + currents were not different between control renal and non-renal DRG neurons. Phasic neurons exhibited higher Na + and K + currents than tonic resulting in shorter APs (3.7 ± 0.3 vs. 6.1 ± 0.6 ms, P   〈  0.01). In neurons incubated with CXCL1, Na + and K + peak current density increased in phasic (Na + : − 969 ± 47 vs. − 758 ± 47 nA/pF, P   〈  0.01; K + : 707 ± 22 vs. 558 ± 31 nA/pF, P   〈  0.01), but were unchanged in tonic neurons. Phasic neurons exposed to CXCL1 showed a broader range of Na + currents ([− 365– − 1429 nA] vs. [− 412– − 4273 nA] ; P   〈  0.05) similar to tonic neurons. After CXCL1 exposure, significant changes in phasic neurons were observed in sodium activation/inactivation as well as a wider distribution of Na + currents characteristic of tonic neurons. These findings indicate a subgroup of tonic neurons besides mere tonic or phasic neurons exists able to exhibit a phasic activity pattern under pathological conditions.
    Type of Medium: Online Resource
    ISSN: 0031-6768 , 1432-2013
    URL: Article
    DOI: 10.1007/s00424-023-02852-6
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1463014-X
    SSG: 12
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  • 9
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    Tolvaptan treatment in an adult Fontan patient with protein-losing enteropathy: a serial 23 Na-MRI investigation
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Chronic Disease Vol. 12 ( 2021-01), p. 204062232110040-
    Details
    In: Therapeutic Advances in Chronic Disease, SAGE Publications, Vol. 12 ( 2021-01), p. 204062232110040-
    Abstract: Protein-losing enteropathy (PLE) is a severe complication of the univentricular Fontan circulation and associated with disturbances in salt and water homeostasis. Fontan patients with PLE have a poor prognosis, with increased morbidity and mortality. Due to limited therapeutic strategies, patients are often treated only symptomatically. Methods: We report our first experience of Tolvaptan (TLV) treatment in a Fontan patient with PLE, severe volume retention and hyponatraemia, refractory to conventional diuretic therapy. In addition to clinical parameters, we monitored drug effects including tissue sodium and volume status via serial 23 Na-magnetic resonance imaging ( 23 Na-MRI) and bioimpedance spectroscopy compared with age-matched controls. Results: 23 Na-MRI identified elevated tissue sodium, which decreased under TLV treatment, as well as volume status, while serum sodium increased and the patient’s symptoms improved. During long-term treatment, we were able to differentiate between sodium and volume status in our patient, suggesting that TLV uncoupled body sodium from water. Conclusion: TLV in addition to loop diuretics improved clinical symptoms of PLE and lowered tissue sodium overload. Long-term effects should be further evaluated in Fontan patients.
    Type of Medium: Online Resource
    ISSN: 2040-6223 , 2040-6231
    URL: Article
    DOI: 10.1177/20406223211004005
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2554816-5
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  • 10
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    The SGLT2 inhibitor empagliflozin reduces tissue sodium content in patients with chronic heart failure: results from a placebo-controlled randomised trial
    Springer Science and Business Media LLC ; 2023
    In:  Clinical Research in Cardiology Vol. 112, No. 1 ( 2023-01), p. 134-144
    Details
    In: Clinical Research in Cardiology, Springer Science and Business Media LLC, Vol. 112, No. 1 ( 2023-01), p. 134-144
    Abstract: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardiovascular protective properties in addition to the metabolic effects and represent a cornerstone of treating patients with chronic heart failure (CHF). We hypothesised that empagliflozin reduces tissue sodium content in patients with CHF. Methods In a double-blind, randomised (2:1), placebo-controlled, parallel-group, clinical trial, 74 patients with NYHA class II–III CHF and an ejection fraction of 49% or less received empagliflozin 10 mg once daily or placebo for 3 months. In each patient, tissue sodium content of the lower leg was assessed non-invasively by sodium-MRI ( 23 Na-MRI) at baseline, after 1 and 3 months of treatment. Results After 1 and 3 months treatment with empagliflozin ( n  = 48), a significant decrease in skin sodium content was observed (1 month: 22.8 ± 6.1 vs. 21.6 ± 6.0 AU, p  = 0.039; 3 months: 22.9 ± 6.1 vs. 21.6 ± 6.1 AU, p  = 0.013), while there was no change in muscle sodium and muscle water content. In direct comparison, the change in skin sodium content between baseline and 3 months was − 1.3 ± 3.5 AU in the empagliflozin group versus 0.6 ± 3.5 AU in the placebo group ( p for between-group difference = 0.022). No significant difference regarding change in muscle sodium and in muscle water content was observed after 3 months treatment between the two groups. Conclusion This trial showed a significant decrease in skin sodium content after 1 and 3 months of treatment with empagliflozin. The decrease in skin sodium content may reflect a decrease in subclinical micro-oedema or/and in non-osmotic bound tissue sodium, both reported to impair left ventricular function. Trial registration number NCT03128528 ( http://www.clinicaltrials.gov ). Trial registration date 25th April 2017.
    Type of Medium: Online Resource
    ISSN: 1861-0684 , 1861-0692
    URL: Article
    DOI: 10.1007/s00392-022-02119-7
    RVK:
    XA 37040
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2218331-0
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