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  1. Article ; Online: Pharmacological suppression of endogenous glucocorticoid synthesis attenuated blood pressure and heart rate response to acute restraint in Wistar rats.

    Bencze, M / Vavřínová, A / Zicha, J / Behuliak, M

    Physiological research

    2020  Volume 69, Issue 3, Page(s) 415–426

    Abstract: Glucocorticoids (GCS) are known to modulate cardiovascular response during stress conditions. The present study was aimed to test the hypothesis that permissive and/or stimulating effect of GCs is essential for the maintenance of peripheral vascular ... ...

    Abstract Glucocorticoids (GCS) are known to modulate cardiovascular response during stress conditions. The present study was aimed to test the hypothesis that permissive and/or stimulating effect of GCs is essential for the maintenance of peripheral vascular resistance and for the adequate response of cardiovascular system to stressor exposure. The effects of acute pharmacological adrenalectomy (PhADX) on humoral and cardiovascular parameters were studied in adult Wistar rats under the basal conditions and during the acute restraint stress. Acute PhADX was performed by the administration of metyrapone and aminoglutethimide (100 mg/kg s.c. of each drug) resulting in a suppression of endogenous glucocorticoid synthesis. Blood pressure (BP), heart rate (HR) and core body temperature were measured using radiotelemetry. BP responses to administration of vasoactive agents were determined in pentobarbital-anesthetized animals. PhADX considerably attenuated stress-induced increase of BP, HR and core body temperature. PhADX did not abolish BP and HR lowering effects of ganglionic blocker pentolinium indicating preserved sympathetic function in PhADX rats. BP response to exogenous norepinephrine administration was attenuated in PhADX rats, suggesting reduced sensitivity of cardiovascular system. Suppression of corticosterone synthesis by PhADX increased basal plasma levels of ACTH, aldosterone and plasma renin activity in unstressed animals but there was no further increase of these hormones following stressor exposure. In conclusion, PhADX attenuated stress-induced rise of blood pressure, heart rate and core body temperature indicating an important permissive and/or stimulating role of glucocorticoids in the maintenance of the adequate response of cardiovascular system and thermoregulation to several stimuli including acute exposure to stressor.
    MeSH term(s) Adrenalectomy ; Aminoglutethimide/pharmacology ; Animals ; Antimetabolites/pharmacology ; Aromatase Inhibitors/pharmacology ; Blood Pressure/drug effects ; Disease Models, Animal ; Glucocorticoids/antagonists & inhibitors ; Glucocorticoids/biosynthesis ; Heart Rate/drug effects ; Male ; Metyrapone/pharmacology ; Rats ; Rats, Wistar ; Restraint, Physical/physiology ; Vascular Resistance/drug effects
    Chemical Substances Antimetabolites ; Aromatase Inhibitors ; Glucocorticoids ; Aminoglutethimide (0O54ZQ14I9) ; Metyrapone (ZS9KD92H6V)
    Language English
    Publishing date 2020-05-29
    Publishing country Czech Republic
    Document type Journal Article
    ZDB-ID 1073141-6
    ISSN 1802-9973 ; 0369-9463 ; 0862-8408
    ISSN (online) 1802-9973
    ISSN 0369-9463 ; 0862-8408
    DOI 10.33549/physiolres.934432
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Changes in cardiovascular autonomic control induced by chronic inhibition of acetylcholinesterase during pyridostigmine or donepezil treatment of spontaneously hypertensive rats.

    Bencze, Michal / Boroš, Almos / Behuliak, Michal / Vavřínová, Anna / Vaněčková, Ivana / Zicha, Josef

    European journal of pharmacology

    2024  Volume 971, Page(s) 176526

    Abstract: Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of ... ...

    Abstract Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors - pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.
    MeSH term(s) Rats ; Animals ; Rats, Inbred SHR ; Pyridostigmine Bromide/pharmacology ; Acetylcholinesterase ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/therapeutic use ; Donepezil/pharmacology ; Rats, Inbred WKY ; Hypertension/drug therapy ; Blood Pressure ; Heart Rate ; Atropine Derivatives
    Chemical Substances Pyridostigmine Bromide (KVI301NA53) ; methylatropine (80719I460H) ; Acetylcholinesterase (EC 3.1.1.7) ; Cholinesterase Inhibitors ; Donepezil (8SSC91326P) ; Atropine Derivatives
    Language English
    Publishing date 2024-03-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2024.176526
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  3. Article ; Online: Excitation-contraction coupling and excitation-transcription coupling in blood vessels: their possible interactions in hypertensive vascular remodeling.

    Misárková, E / Behuliak, M / Bencze, M / Zicha, J

    Physiological research

    2016  Volume 65, Issue 2, Page(s) 173–191

    Abstract: Vascular smooth muscle cells (VSMC) display considerable phenotype plasticity which can be studied in vivo on vascular remodeling which occurs during acute or chronic vascular injury. In differentiated cells, which represent contractile phenotype, there ... ...

    Abstract Vascular smooth muscle cells (VSMC) display considerable phenotype plasticity which can be studied in vivo on vascular remodeling which occurs during acute or chronic vascular injury. In differentiated cells, which represent contractile phenotype, there are characteristic rapid transient changes of intracellular Ca(2+) concentration ([Ca(2+)]i), while the resting cytosolic [Ca(2+)]i concentration is low. It is mainly caused by two components of the Ca(2+) signaling pathways: Ca(2+) entry via L-type voltage-dependent Ca(2+) channels and dynamic involvement of intracellular stores. Proliferative VSMC phenotype is characterized by long-lasting [Ca(2+)]i oscillations accompanied by sustained elevation of basal [Ca(2+)]i. During the switch from contractile to proliferative phenotype there is a general transition from voltage-dependent Ca(2+) entry to voltage-independent Ca(2+) entry into the cell. These changes are due to the altered gene expression which is dependent on specific transcription factors activated by various stimuli. It is an open question whether abnormal VSMC phenotype reported in rats with genetic hypertension (such as spontaneously hypertensive rats) might be partially caused by a shift from contractile to proliferative VSMC phenotype.
    MeSH term(s) Animals ; Blood Vessels/metabolism ; Blood Vessels/pathology ; Calcium Signaling/physiology ; Excitation Contraction Coupling/physiology ; Humans ; Hypertension/metabolism ; Hypertension/pathology ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/pathology ; Signal Transduction/physiology ; Transcription, Genetic/physiology ; Vascular Remodeling/physiology
    Language English
    Publishing date 2016-04-14
    Publishing country Czech Republic
    Document type Journal Article ; Review
    ZDB-ID 1073141-6
    ISSN 1802-9973 ; 0369-9463 ; 0862-8408
    ISSN (online) 1802-9973
    ISSN 0369-9463 ; 0862-8408
    DOI 10.33549/physiolres.933317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Acute and chronic role of nitric oxide, renin-angiotensin system and sympathetic nervous system in the modulation of calcium sensitization in Wistar rats.

    Brunová, A / Bencze, M / Behuliak, M / Zicha, J

    Physiological research

    2015  Volume 64, Issue 4, Page(s) 447–457

    Abstract: Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible ... ...

    Abstract Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible modulation of calcium sensitization by the above vasoactive systems, we studied the influence of acute and chronic blockade of particular vasoactive systems on blood pressure (BP) changes elicited in conscious normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used throughout this study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response to fasudil, the effect being considerably augmented in rats deprived of endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin modified BP response to fasudil less than the acute NOS inhibition. The chronic NOS inhibition caused moderate BP elevation and a more pronounced augmentation of fasudil-induced BP changes compared to the effect of acute NOS inhibition. This indicates both short-term and long-term NO-dependent attenuation of calcium sensitization. Long-term inhibition of RAS by captopril caused a significant attenuation of BP changes elicited by fasudil. In contrast, a long-term attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had no effect on BP response to fasudil, suggesting the absence of SNS does not affect calcium sensitization in vascular smooth muscle of normotensive rats. In conclusion, renin-angiotensin system contributes to the long-term increase of calcium sensitization and its effect is counterbalanced by nitric oxide which decreases calcium sensitization in Wistar rats.
    MeSH term(s) Adaptation, Physiological/physiology ; Animals ; Blood Pressure/physiology ; Calcium/metabolism ; Male ; Nitric Acid/metabolism ; Rats ; Rats, Wistar ; Renin-Angiotensin System/physiology ; Sympathetic Nervous System/physiology ; Vascular Resistance/physiology ; Vasoconstriction/physiology
    Chemical Substances Nitric Acid (411VRN1TV4) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2015-08-05
    Publishing country Czech Republic
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1073141-6
    ISSN 1802-9973 ; 0369-9463 ; 0862-8408
    ISSN (online) 1802-9973
    ISSN 0369-9463 ; 0862-8408
    DOI 10.33549/physiolres.933094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The impact of four different classes of anesthetics on the mechanisms of blood pressure regulation in normotensive and spontaneously hypertensive rats.

    Bencze, M / Behuliak, M / Zicha, J

    Physiological research

    2013  Volume 62, Issue 5, Page(s) 471–478

    Abstract: Most anesthetics induce characteristic hemodynamic changes leading to blood pressure (BP) reduction but the role of renin-angiotensin system (RAS), sympathetic nervous system (SNS) and nitric oxide (NO) synthesis in this BP reduction is unknown. We ... ...

    Abstract Most anesthetics induce characteristic hemodynamic changes leading to blood pressure (BP) reduction but the role of renin-angiotensin system (RAS), sympathetic nervous system (SNS) and nitric oxide (NO) synthesis in this BP reduction is unknown. We therefore studied the influence of four widely used anesthetics - pentobarbital (P), isoflurane (ISO), ketamine-xylazine (KX) and chloralose-urethane (CU) - on the participation of these vasoactive systems in BP maintenance. BP effects elicited by the acute sequential blockade of RAS (captopril), SNS (pentolinium) and NO synthase (L-NAME) were compared in conscious and anesthetized Wistar or spontaneously hypertensive rats (SHR). Except for pentobarbital all studied anesthetics evidenced by diminished BP responses to pentolinium. The absolute pentolinium-induced BP changes were always greater in SHR than Wistar rats. KX anesthesia eliminated BP response to pentolinium and considerably enhanced BP response to NO synthase inhibition in SHR. In both rat strains the anesthesia with ISO or CU augmented BP response to captopril, decreased BP response to pentolinium and attenuated BP response to NO synthase inhibition. In conclusion, pentobarbital anesthesia had a modest influence on BP level and its maintenance by the above vasoactive systems. Isoflurane and chloralose-urethane anesthesia may be used in cardiovascular experiments if substantial BP decrease due to altered contribution of RAS, SNS and NO to BP regulation does not interfere with the respective research aim. Major BP reduction (namely in SHR) due to a complete SNS absence is a major drawback of ketamine-xylazine anesthesia.
    MeSH term(s) Anesthetics/pharmacology ; Anesthetics, Combined/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Blood Pressure/drug effects ; Chloralose/pharmacology ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Ganglionic Blockers/pharmacology ; Hypertension/metabolism ; Hypertension/physiopathology ; Isoflurane/pharmacology ; Ketamine/pharmacology ; Male ; Nitric Oxide/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Pentobarbital/pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Renin-Angiotensin System/drug effects ; Sympathetic Nervous System/drug effects ; Sympathetic Nervous System/physiopathology ; Urethane/pharmacology ; Xylazine/pharmacology
    Chemical Substances Anesthetics ; Anesthetics, Combined ; Angiotensin-Converting Enzyme Inhibitors ; Enzyme Inhibitors ; Ganglionic Blockers ; Chloralose (238BZ29MUE) ; Xylazine (2KFG9TP5V8) ; Nitric Oxide (31C4KY9ESH) ; Urethane (3IN71E75Z5) ; Ketamine (690G0D6V8H) ; Isoflurane (CYS9AKD70P) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Pentobarbital (I4744080IR)
    Language English
    Publishing date 2013-09-10
    Publishing country Czech Republic
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1073141-6
    ISSN 1802-9973 ; 0369-9463 ; 0862-8408
    ISSN (online) 1802-9973
    ISSN 0369-9463 ; 0862-8408
    DOI 10.33549/physiolres.932637
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Perspectives on skeletal muscle stem cells.

    Relaix, F / Bencze, M / Borok, M J / Der Vartanian, A / Gattazzo, F / Mademtzoglou, D / Perez-Diaz, S / Prola, A / Reyes-Fernandez, P C / Rotini, A / Taglietti

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 692

    Abstract: Skeletal muscle has remarkable regeneration capabilities, mainly due to its resident muscle stem cells (MuSCs). In this review, we introduce recently developed technologies and the mechanistic insights they provide to the understanding of MuSC biology, ... ...

    Abstract Skeletal muscle has remarkable regeneration capabilities, mainly due to its resident muscle stem cells (MuSCs). In this review, we introduce recently developed technologies and the mechanistic insights they provide to the understanding of MuSC biology, including the re-definition of quiescence and G
    MeSH term(s) Animals ; Disease Models, Animal ; Humans ; Muscle, Skeletal/cytology ; Muscle, Skeletal/physiology ; Muscular Diseases/physiopathology ; Muscular Diseases/therapy ; Regeneration/physiology ; Regenerative Medicine/methods ; Stem Cell Transplantation/methods ; Stem Cells/physiology
    Language English
    Publishing date 2021-01-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-20760-6
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  7. Article ; Online: The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats.

    Pistikova, A / Brozka, H / Bencze, M / Radostova, D / Vales, K / Stuchlik, A

    Physiological research

    2017  Volume 66, Issue 5, Page(s) 881–887

    Abstract: The dentate gyrus of the hippocampus is one of the few places in the brain where neurogenesis occurs in adulthood. Nowadays, an increasing number of children and young adults are affected by hypertension, one of the factors in the development of ... ...

    Abstract The dentate gyrus of the hippocampus is one of the few places in the brain where neurogenesis occurs in adulthood. Nowadays, an increasing number of children and young adults are affected by hypertension, one of the factors in the development of cerebrovascular diseases and age-related cognitive deficits. Since these cognitive deficits are often hippocampus-dependent, it is possible that hypertension exerts this effect via decreasing adult neurogenesis which has been shown to be essential for a range of cognitive tasks. We used spontaneously hypertensive rats, which develop hypertension in the first weeks of life. Half of them were treated with the antihypertensive drug captopril. We found that the drug-induced lowering of blood pressure in this period did not affect the rate of adult neurogenesis. In a second experiment, we used another animal model of hypertension - salt-sensitive and salt-resistant strains of Dahl rats. A high-salt diet induces hypertension in the salt-sensitive strain, but not in the salt-resistant strain. The high-salt diet led to salt-induced hypertension, but did not affect the level of adult neurogenesis in the dentate gyrus of the hippocampus. We conclude that hypertension does not significantly affect the rate of hippocampal neurogenesis in young adult rats.
    MeSH term(s) Age Factors ; Animals ; Blood Pressure/physiology ; Hippocampus/pathology ; Hippocampus/physiology ; Hypertension/pathology ; Hypertension/physiopathology ; Male ; Neurogenesis/physiology ; Random Allocation ; Rats ; Rats, Inbred Dahl ; Rats, Inbred SHR
    Language English
    Publishing date 2017-07-18
    Publishing country Czech Republic
    Document type Journal Article
    ZDB-ID 1073141-6
    ISSN 1802-9973 ; 0369-9463 ; 0862-8408
    ISSN (online) 1802-9973
    ISSN 0369-9463 ; 0862-8408
    DOI 10.33549/physiolres.933562
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  8. Article ; Online: Immunolabelling Myofiber Degeneration in Muscle Biopsies.

    Bencze, Maximilien / Periou, Baptiste / Baba-Amer, Yasmine / Authier, Francois J

    Journal of visualized experiments : JoVE

    2019  , Issue 154

    Abstract: The necrosis of muscle fibres (myonecrosis) plays a central role in the pathogenesis of several muscle conditions, including muscular dystrophies. Therapeutic options addressing the causes of muscular dystrophy pathogenesis are expected to alleviate ... ...

    Abstract The necrosis of muscle fibres (myonecrosis) plays a central role in the pathogenesis of several muscle conditions, including muscular dystrophies. Therapeutic options addressing the causes of muscular dystrophy pathogenesis are expected to alleviate muscle degeneration. Therefore, a method to assay and quantify the extent of cell death in muscle biopsies is needed. Conventional methods to observe myofiber degeneration in situ are either poorly quantitative or rely on the injection of vital dyes. In this article, an immunofluorescence protocol is described that stains necrotic myofibers by targeting immunoglobulin G (IgG) uptake by myofibers. The IgG uptake method is based on cell features characterizing the necrotic demise, including 1) the loss of plasma membrane integrity with the release of damage-associated molecular patterns and 2) the uptake of plasmatic proteins. In murine cross-sections, the co-immunolabelling of myofibers, extracellular matrix proteins, and mouse IgG allows clean and straightforward identification of myofibers with necrotic fate. This simple method is suitable for quantitative analysis and applicable to all species, including human samples, and does not require the injection of vital dye. The staining of necrotic myofibers by IgG uptake can also be paired with other co-immunolabelling.
    MeSH term(s) Animals ; Biopsy ; Cell Death ; Cell Membrane/metabolism ; Humans ; Immunoglobulins/metabolism ; Mice ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/pathology ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Muscular Dystrophies/metabolism ; Muscular Dystrophies/pathology ; Necrosis
    Chemical Substances Immunoglobulins
    Language English
    Publishing date 2019-12-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/59754
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  9. Article ; Online: Which sympathoadrenal abnormalities of adult spontaneously hypertensive rats can be traced to a prehypertensive stage?

    Vavřínová, Anna / Behuliak, Michal / Bencze, Michal / Vaněčková, Ivana / Zicha, Josef

    Hypertension research : official journal of the Japanese Society of Hypertension

    2019  Volume 42, Issue 7, Page(s) 949–959

    Abstract: Alterations of sympathoadrenal and sympathoneural systems have been suggested to be involved in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). To evaluate the ontogenetic changes of these systems, mRNA and protein expressions ... ...

    Abstract Alterations of sympathoadrenal and sympathoneural systems have been suggested to be involved in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). To evaluate the ontogenetic changes of these systems, mRNA and protein expressions of catecholaminergic system genes were measured in adrenal glands and sympathetic ganglia, and the catecholamine levels were determined in adrenal glands, sympathetic ganglia and plasma of prehypertensive (4-week-old) and hypertensive (24-week-old) SHR. Vascular sympathetic innervation was visualized in the femoral artery by glyoxylic acid. In the adrenal glands of prehypertensive SHR, the expression of catecholamine biosynthetic enzymes Ddc, Dbh and Pnmt was lower than in aged-matched Wistar-Kyoto rats. In contrast, the adrenal content of dopamine, noradrenaline and adrenaline was higher in prehypertensive SHR (141%, 123% and 120% of Wistar-Kyoto rats, respectively, p < 0.01). In the adrenal glands of adult SHR, the expression of catecholamine biosynthetic enzymes Th, Ddc, Dbh and Pnmt was decreased along the amounts of dopamine and noradrenaline (50% and 38%, respectively, p < 0.001). The expression levels of Ddc and Dbh enzymes were also downregulated in the sympathetic ganglia of both prehypertensive and adult SHR. At both ages, the density of sympathetic innervation was twofold higher in SHR compared to Wistar-Kyoto rats (p < 0.001). In conclusion, adrenal catecholamine content was increased in prehypertensive SHR, whereas it was reduced in SHR with established hypertension. Surprisingly, downregulation of catecholamine biosynthetic enzymes was observed in both the adrenal medulla and sympathetic ganglia of SHR at both ages. Thus, this downregulation might be a compensatory mechanism that counteracts the vascular sympathetic hyperinnervation seen in SHR of both ages.
    MeSH term(s) Adrenal Glands/metabolism ; Animals ; Autonomic Nervous System/physiopathology ; Dopamine/metabolism ; Epinephrine/metabolism ; Hypertension/metabolism ; Hypertension/physiopathology ; Male ; Norepinephrine/metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Tyrosine 3-Monooxygenase/metabolism
    Chemical Substances Tyrosine 3-Monooxygenase (EC 1.14.16.2) ; Dopamine (VTD58H1Z2X) ; Norepinephrine (X4W3ENH1CV) ; Epinephrine (YKH834O4BH)
    Language English
    Publishing date 2019-01-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1175297-x
    ISSN 1348-4214 ; 0916-9636
    ISSN (online) 1348-4214
    ISSN 0916-9636
    DOI 10.1038/s41440-018-0198-y
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  10. Article ; Online: Receptor interacting protein kinase-3 mediates both myopathy and cardiomyopathy in preclinical animal models of Duchenne muscular dystrophy.

    Bencze, Maximilien / Periou, Baptiste / Punzón, Isabel / Barthélémy, Inès / Taglietti, Valentina / Hou, Cyrielle / Zaidan, Louai / Kefi, Kaouthar / Blot, Stéphane / Agbulut, Onnik / Gervais, Marianne / Derumeaux, Geneviève / Authier, François-Jérôme / Tiret, Laurent / Relaix, Fréderic

    Journal of cachexia, sarcopenia and muscle

    2023  Volume 14, Issue 6, Page(s) 2520–2531

    Abstract: Background: Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder, culminating in a complete loss of ambulation, hypertrophic cardiomyopathy and a fatal cardiorespiratory failure. Necroptosis is the form of necrosis that is ... ...

    Abstract Background: Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder, culminating in a complete loss of ambulation, hypertrophic cardiomyopathy and a fatal cardiorespiratory failure. Necroptosis is the form of necrosis that is dependent upon the receptor-interacting protein kinase (RIPK) 3; it is involved in several inflammatory and neurodegenerative conditions. We previously identified RIPK3 as a key player in the acute myonecrosis affecting the hindlimb muscles of the mdx dystrophic mouse model. Whether necroptosis also mediates respiratory and heart disorders in DMD is currently unknown.
    Methods: Evidence of activation of the necroptotic axis was examined in dystrophic tissues from Golden retriever muscular dystrophy (GRMD) dogs and R-DMDdel52 rats. A functional assessment of the involvement of necroptosis in dystrophic animals was performed on mdx mice that were genetically depleted for RIPK3. Dystrophic mice aged from 12 to 18 months were analysed by histology and molecular biology to compare the phenotype of muscles from mdxRipk3
    Results: RIPK3 expression in sartorius and biceps femoris muscles from GRMD dogs positively correlated to myonecrosis levels (r = 0.81; P = 0.0076). RIPK3 was also found elevated in the diaphragm (P ≤ 0.05). In the slow-progressing heart phenotype of GRMD dogs, the phosphorylated form of RIPK1 at the Serine 161 site was dramatically increased in cardiomyocytes. A similar p-RIPK1 upregulation characterized the cardiomyocytes of the severe DMDdel52 rat model, associated with a marked overexpression of Ripk1 (P = 0.007) and Ripk3 (P = 0.008), indicating primed activation of the necroptotic pathway in the dystrophic heart. MdxRipk3
    Conclusions: Our data highlight molecular and histological evidence that the necroptotic pathway is activated in degenerative tissues from dystrophic animal models, including the diaphragm and the heart. We also provide the genetic proof of concept that selective inhibition of necroptosis in dystrophic condition improves both histological features of muscles and cardiac function, suggesting that prevention of necroptosis is susceptible to providing multiorgan beneficial effects for DMD.
    MeSH term(s) Animals ; Dogs ; Mice ; Rats ; Cardiomyopathies/genetics ; Cardiomyopathies/metabolism ; Disease Models, Animal ; Mice, Inbred mdx ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/metabolism ; Protein Kinases ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
    Chemical Substances Protein Kinases (EC 2.7.-) ; Ripk3 protein, mouse (EC 2.7.11.1) ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2023-11-01
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2586864-0
    ISSN 2190-6009 ; 2190-5991
    ISSN (online) 2190-6009
    ISSN 2190-5991
    DOI 10.1002/jcsm.13265
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