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  • 1
    In: The FASEB Journal, Wiley, Vol. 34, No. S1 ( 2020-04), p. 1-1
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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  • 2
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    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of Hypertension Vol. 41, No. Suppl 3 ( 2023-06), p. e75-
    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
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2017684-3
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  • 3
    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
    RVK:
    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
    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
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1463014-X
    SSG: 12
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  • 5
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 74, No. Suppl_1 ( 2019-09)
    Abstract: Afferent renal nerve pathways are likely involved the development of salt sensitive hypertension. We recently reported that intrarenal NaCl elicited a long-lasting sympatho-depression via a neuro-humoral TRPV1 dependent and tachykinin mediated renal afferent nerve pathway. We now wanted to test the hypothesis that high sodium intake impairs this afferent sympatho-depressory mechanism. Respective groups were put on tap water, 0.9 % saline for drinking or chow containing 8% NaCl. Cultured dorsal root ganglion neurons (DRG Th11-L2) of rats with renal afferents were investigated in current clamp mode to assess action potential generation during current injection. Rats were equipped with femoral catheters for blood pressure (BP) & heart rate (HR) assessment, drug application, a renal arterial catheter for intrarenal administration (IRA) of NaCl boli (10 % NaCl, 10 μl) or Capsaicin (CAP 3.3, 6.6, 10, 33*10-7 M, 10 μl) and a bipolar electrode for renal sympathetic nerve activity (RSNA) recordings; eventually an intravenous (iv) bolus of the NK1-receptor blocker RP67580 (10*10-3M, 15 μl) was administered. Results are mean±SEM. In neurons from rats on high salt diet, but not on 0.9 % saline or controls the relation of tonic highly active neurons to less active neurons shifted towards less active units (tap water -tonic/phasic: 22/15; saline - tonic/phasic: 28/18; 8% high salt - tonic/phasic: 14/21* P 〈 0.05). However, cultured tonic renal neurons from rats on 0.9% saline or on high salt diet exhibited increased action potential (AP) production upon stimulation (control 13,3+/4 APs/600ms vs. saline 19,8+/-2,33* APs/600ms vs. high salt diet 22,2*+/-4,54 APs/600ms, control vs. experimental *p 〈 0.05, mean+/-SEM). ). 10% NaCl boli IRA induced decreases of RSNA from baseline 4.1±0.6 μV*sec to 2.2±0.8 μV*sec impaired in rats on 8% NaCl. (Suppressed RSNA unmasked in all groups by an i.v. NK1-inhibitor) In rats on high salt diet highly active tonic neurons with renal afferents in vitro decreased at the expense of less active phasic neurons in spite of tonic neurons producing more action potentials upon stimulation. The sodium inducible long-lasting sympatho-depression via a neuro-humoral tachykinin mediated afferent renal nerve pathway was eventually impaired.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2094210-2
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  • 6
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 46, No. 3 ( 2021), p. 331-341
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Angiotensin II (Ang II) and the renal sympathetic nervous system exert a strong influence on renal sodium and water excretion. We tested the hypothesis that already low doses of an Ang II inhibitor (candesartan) will result in similar effects on tubular sodium and water reabsorption in congestive heart failure (CHF) as seen after renal denervation (DNX). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Measurement of arterial blood pressure, heart rate (HR), renal sympathetic nerve activity (RSNA), glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, and urinary sodium. To assess neural control of volume homeostasis, 21 days after the induction of CHF via myocardial infarction rats underwent volume expansion (0.9% NaCL; 10% body weight) to decrease RSNA. CHF rat and controls with or without DNX or pretreated with the Ang II type-1 receptor antagonist candesartan (0.5 ug i.v.) were studied. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 CHF rats excreted only 68 + 10.2% of the volume load (10% body weight) in 90 min. CHF rats pretreated with candesartan or after DNX excreted from 92 to 103% like controls. Decreases of RSNA induced by volume expansion were impaired in CHF rats but unaffected by candesartan pointing to an intrarenal drug effect. GFR and RPF were not significantly different in controls or CHF. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The prominent function of increased RSNA – retaining salt and water – could no longer be observed after renal Ang II receptor blockade in CHF rats.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482922-8
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  • 7
    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
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 8
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
    Abstract: Afferent renal nerve pathways likely play a role in salt sensitive hypertension. We recently reported that high salt diet (HS) impairs these afferent renal pathways in rats. Now we tested the hypothesis that during HS a decrease in sensitivity of renal afferent neurons is prevented by the SGLT2 inhibitor empagiflozin.Respective groups of rats were put on HS containing 8% NaCl or a normal diet. Two groups (HS, controls) received empagiflozin 20 mg/kg BW/day orally. Renal neurons were retrogradely labeled with DiI. In culture, labeled dorsal root ganglion neurons (DRG Th11-L2) with renal afferents were investigated electrophysiologically 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 neurons from rats on HS, the relation of tonic highly active neurons to less active phasic neurons shifted consistently towards phasic units (63,8% tonic neurons in controls vs. 42%* on HS, *p 〈 0.05, z-test). However, continuous treatment with empagiflozin preserved the proportion of tonic neurons as in controls (67,9% on HS with concomitant administration of empagiflozin). In controls, empagiflozin did not affect the proportion of tonic to phasic neurons (63,8% tonic neurons in controls vs. 67,9% on HS & empagliflozin, p=0.7, z-test). Blood pressure and heart rate were not altered by HS and/or treatment with any chosen dose of empagiflozin.In rats, chronically elevated sodium intake (8% NaCl) reduced the sensitivity and stimulability of renal afferent DRG neurons. Under these circumstances, concomitant treatment with the SGLT2 inhibitor empagiflozin preserved the function of renal afferent DRG neurons. SGLT 2 inhibitors may help to treat dysfunction of renal innervation in cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 9
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 74, No. Suppl_1 ( 2019-09)
    Abstract: Sodium can be accumulated without commensurate water retention in the skin (non-osmotic sodium storage). Macrophages play a pivotal role in this context and their depletion can induce salt-sensitive hypertension (ssHTN). On the other hand renal afferent peptidergic nerves are involved in ssHTN. Since the skin is also densely innervated by afferent peptidergic nerves we hypothesized that high salt diet might enhance the release of neuropeptides from these nerve fibers. In a cross-over design, two groups of rats (n=6, each) were fed either low salt diet (LS; 0.2%) with free access to tab water for 14 days or high salt diet (HS; 8%) with free access to 0.9% saline as drinking water. After 14 days a skin sample (3x3mm) of the groin area was excised, and the diet was switched for another 14 days. Then a contralateral skin sample was taken. Tissue analyzed in an organ-bath and calcitonin gene related peptide (CGRP) content in the supernatant was measured with ELISA. After two baseline measurements within 5 min, the tissue was superfused with hypertonic saline (4.5%) for 5 min, and three further samples of the supernatant were taken every 5 min. Baseline CGRP release was similar with both diets (LS 11.9±1.5 vs HS 13.6±1.5ng/g skin). Maximum release was higher with HS diet (LS 17.5±1.8 vs HS 29.8±1.3ng/g skin; P 〈 0.05). After diet switch the results were similar: baseline LS 9.4±1.2 vs HS 10.1±, however, in rats previously on HS diet release tended to be higher with LS diet, nevertheless with HS diet the release was higher again (LS 19.7±2.1 vs HS 29.3±1.7; P 〈 0.05). High sodium diet sensitized neuropeptide release from peptidergic sensory nerves in the skin. Hence peptidergic afferent nerves might be an integrated body-wide system involved in sodium handling in very different target areas like skin and kidney. Putative peptidergic mechanisms (vasoregulation, chemotaxis) remain to be determined in this respect.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2094210-2
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Journal of Hypertension Vol. 39, No. Supplement 1 ( 2021-04), p. e15-
    In: Journal of Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 39, No. Supplement 1 ( 2021-04), p. e15-
    Type of Medium: Online Resource
    ISSN: 0263-6352 , 1473-5598
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2017684-3
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