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1.
Neurosci Bull ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641986

RESUMO

Toll-like receptor 4 (TLR4) and cellular Src (c-Src) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension. Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension. This resulted in higher levels of TLR4, activated c-Src, pro-inflammatory cytokines, oxidative stress, and arterial pressure. Infusion of a TLR4 blocker into the hypothalamic paraventricular nucleus (PVN) decreased the activated c-Src, while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B, pro-inflammatory cytokines, and oxidative stress. Our findings suggest that a long-term high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src, which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species. Therefore, inhibiting central c-Src activity may be a new target for treating hypertension.

2.
Sci Rep ; 7: 43107, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28338001

RESUMO

Brain renin-angiotensin system (RAS) could regulate oxidative stress in the paraventricular nucleus (PVN) in the development of hypertension. This study was designed to explore the precise mechanisms of RAS acting on reactive oxygen species (ROS) in salt-induced hypertension. Male Wistar rats were administered with a high-salt diet (HS, 8.0% NaCl) for 8 weeks to induced hypertension. Those rats were received PVN infusion of AT1R antagonist losartan (LOS, 10 µg/h) or microinjection of small interfering RNAs for protein kinase C γ (PKCγ siRNA) once a day for 2 weeks. High salt intake resulted in higher levels of AT1R, PKCγ, Rac1 activity, superoxide and malondialdehyde (MDA) activity, but lower levels of copper/zinc superoxide dismutase (Cu/Zn-SOD), superoxide dismutase (SOD) and glutathione (GSH) in PVN than control animals. PVN infusion of LOS not only attenuated the PVN levels of AT1R, PKCγ, Rac1 activity, superoxide and decreased the arterial pressure, but also increased the PVN antioxidant capacity in hypertension. PVN microinjection of PKCγ siRNA had the same effect on LOS above responses to hypertension but no effect on PVN level of AT1R. These results, for the first time, identified that the precise signaling pathway of RAS regulating ROS in PVN is via AT1R/PKCγ/Rac1 in salt-induced hypertension.


Assuntos
Hipertensão/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sistema Renina-Angiotensina , Transdução de Sinais , Animais , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Masculino , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio na Dieta/efeitos adversos , Proteínas rac1 de Ligação ao GTP/metabolismo
3.
Cardiovasc Toxicol ; 16(4): 345-54, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26438340

RESUMO

High-salt-induced inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive hypertension. In this study, we hypothesized that chronic inhibition of nuclear factor-κB (NF-κB) activity in the PVN delays the progression of hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD-like receptor family pyrin domain containing 3) and IL-1ß and attenuating p-IKKß, NF-κB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive hypertensive rats. Dahl salt-sensitive rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks and were treated with bilateral PVN infusion with either vehicle or pyrrolidine dithiocarbamate (PDTC, 5 µg/h), a NF-κB inhibitor via osmotic minipump. The mean arterial pressure and plasma levels of norepinephrine (NE) and epinephrine (EPI) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of p-IKKß, NF-κB p65 activity, Fra-like (Fra-LI) activity (an indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase), NLRP3 and IL-1ß, and lower levels of IL-10 in the PVN than normal diet rats. Bilateral PVN infusions of PDTC attenuated these high-salt-induced changes. These findings suggest that high-salt-induced NF-κB activation in the PVN caused hypertension via sympathoexcitation, which are associated with the increases of NLRP3, IL-1ß and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates NLRP3, IL-1ß and oxidative stress in the PVN and thereby attenuates hypertension.


Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Caspase 1/metabolismo , Hipertensão/prevenção & controle , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Pirrolidinas/administração & dosagem , Cloreto de Sódio na Dieta , Tiocarbamatos/administração & dosagem , Fator de Transcrição RelA/antagonistas & inibidores , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Biomarcadores/sangue , Modelos Animais de Doenças , Epinefrina/sangue , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Quinase I-kappa B/metabolismo , Infusões Parenterais , Interleucina-1beta/metabolismo , Masculino , Norepinefrina/sangue , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/enzimologia , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Fosforilação , Ratos Endogâmicos Dahl , Transdução de Sinais , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Fator de Transcrição RelA/metabolismo
4.
Toxicol Appl Pharmacol ; 284(3): 315-22, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25759242

RESUMO

We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (ß-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy.


Assuntos
Cardiomegalia/prevenção & controle , Citocinas/metabolismo , Hipertensão/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Animais , Pressão Arterial/efeitos dos fármacos , Biomarcadores/metabolismo , Cardiomegalia/etiologia , Cardiomegalia/imunologia , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Hipertensão/complicações , Hipertensão/imunologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Núcleo Hipotalâmico Paraventricular/imunologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo , Fator de Transcrição RelA/metabolismo
5.
Toxicol Appl Pharmacol ; 281(1): 101-8, 2014 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-25223692

RESUMO

We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (ß-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy.


Assuntos
Cardiomegalia/metabolismo , Hipertensão/metabolismo , Neurotransmissores/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Animais , Cardiomegalia/prevenção & controle , Hipertensão/prevenção & controle , Masculino , Neurotransmissores/antagonistas & inibidores , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
6.
Toxicol Appl Pharmacol ; 279(2): 141-9, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24937322

RESUMO

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10µg/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Citocinas/metabolismo , Hipertensão Renovascular/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Lisinopril/administração & dosagem , Bulbo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Hipertensão Renovascular/imunologia , Hipertensão Renovascular/metabolismo , Hipertensão Renovascular/fisiopatologia , Mediadores da Inflamação/sangue , Infusões Parenterais , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Masculino , Bulbo/imunologia , Bulbo/metabolismo , Bulbo/fisiopatologia , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Núcleo Hipotalâmico Paraventricular/imunologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Peptidil Dipeptidase A/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo
7.
Cardiovasc Toxicol ; 13(1): 48-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22971929

RESUMO

Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether renin-angiotensin system (RAS) activation in the hypothalamic paraventricular nucleus (PVN) contributes to the ANG II-induced hypertensive response via interaction with neurotransmitters in the PVN. Rats underwent subcutaneous infusion of ANG II or saline for 4 weeks. These rats were treated for 4 weeks through bilateral PVN infusion with either vehicle or losartan (LOS), an angiotensin II type 1 receptor (AT1-R) antagonist, via osmotic minipump. ANG II infusion resulted in higher levels of glutamate, norepinephrine (NE), AT1-R and pro-inflammatory cytokines (PIC), and lower level of gamma-aminobutyric acid (GABA) in the PVN. Rats receiving ANG II also had higher levels of mean arterial pressure, plasma PIC, NE and aldosterone than control animals. PVN treatment with LOS attenuated these ANG II-induced hypertensive responses. In conclusion, these findings suggest that the RAS activation in the PVN contributes to the ANG II-induced hypertensive response via interaction with PIC and neurotransmitters (glutamate, NE and GABA) in the PVN.


Assuntos
Angiotensina II/toxicidade , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Neurotransmissores/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Renina-Angiotensina/fisiologia , Animais , Masculino , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos
8.
Muscle Nerve ; 45(1): 65-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22190309

RESUMO

INTRODUCTION: The purpose of this study was to evaluate the electrophysiological changes observed in dorsal root ganglion (DRG) neurons in a simulated weightlessness rat model and to assess the mechanisms involved in these changes. METHODS: The simulated weightlessness model was created by hindlimb unloading (HU). Whole-cell patch-clamp recordings, conduction velocity measurement, and ultrastructural observation were performed. RESULTS: In the HU rats, the action potentials had a longer duration and slower falling rate, but there was no significant effect on amplitude or rate of rise. HU also induced lowering of rheobase and of the threshold potential, making the cells more excitable. The conduction velocities in the proximal branches of ganglion cells were also decreased, and some degenerative changes in the myelin sheath were noted. CONCLUSIONS: This study provides evidence of plasticity of DRG neurons induced by HU. The changes observed might contribute to impaired motor performance in rats submitted to HU.


Assuntos
Gânglios Espinais/citologia , Elevação dos Membros Posteriores , Potenciais da Membrana/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Biofísica , Estimulação Elétrica , Feminino , Microscopia Eletrônica de Transmissão , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/ultraestrutura
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(5): 545-9, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21984159

RESUMO

OBJECTIVE: To investigate the effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization. METHODS: The immobilization of rat soleus muscle was induced as a disuse muscle model, and 100 Hz sinusoidal vibration was generated by a vibrator and applied to the immobilized soleus muscle, then the changes of H reflex and M wave in muscle were observed after 14 d. RESULTS: Compared to control, after 14 d of immobilization M(max) in soleus muscle decreased (P<0.01), stimulus threshold and S(max) increased (P<0.01); Hmax and H(max)/M(max) decreased (P<0.05, S(max) increased (P<0.05). Compared to immobilized soleus muscle, after 14 d of immobilization with 100 Hz sinusoidal vibration, the M(max) increased(P<0.01), stimulus threshold and S(Mmax) decreased (P<0.05), H(max) (P<0.01) increased and H(max)/M(max) increased (P<0.05). CONCLUSION: 100 Hz sinusoidal vibration plays a significant antagonist role against the changes in H reflex and M wave in rat soleus muscle following immobilization.


Assuntos
Reflexo H/fisiologia , Elevação dos Membros Posteriores , Músculo Esquelético/fisiologia , Vibração , Animais , Eletromiografia , Feminino , Contração Muscular/fisiologia , Fusos Musculares/fisiologia , Ratos , Ratos Sprague-Dawley
10.
J Electromyogr Kinesiol ; 21(6): 1017-22, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21924624

RESUMO

V-wave, F wave and H-reflex responses of soleus were used to determine neural adaptations to 2-week immobilization and whether muscle vibration intervention during immobilization would attenuate the negative adaptations induced by immobilization. Thirty subjects were divided into the ankle immobilization group and the immobilization with muscle vibration group. Mechanical vibrations with constant low amplitude (0.3mm) were applied (12×4 min daily) with a constant frequency of 100Hz on the soleus muscle of the subjects in vibration group during the ankle immobilization period. Soleus maximal M-wave (Mmax) and H-reflex (Hmax) were evoked at rest. F-wave was recorded by supramaximal stimulation delivered at rest and V-wave during maximum voluntary contraction (MVC). The EMG during MVC was represented by its root-mean-square (RMS) value. Each subject was examined before and after 2 weeks of immobilization. Results showed that following 2 weeks of immobilization, Mmax, Hmax and F wave all did not change with immobilization in either group (P>0.05). After 2 weeks of immobilization, significant reductions in V/Mmax (of 30.78%) (P<0.01) and EMG RMS (24.82%) (P<0.001) were found in the immobilization group. However, no significant changes occurred in the immobilization with muscle vibration group. Such findings suggested that 2 weeks of immobilization resulted in neural impairments as evidenced by the reduction in EMG and V wave, and that such decrease was prevented by the intervention of muscle vibration during the immobilization period.


Assuntos
Imobilização/efeitos adversos , Contração Muscular , Músculo Esquelético/fisiopatologia , Doenças Musculares/prevenção & controle , Doenças Musculares/fisiopatologia , Reflexo , Vibração/uso terapêutico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Doenças Musculares/etiologia , Resultado do Tratamento , Adulto Jovem
11.
Sheng Li Xue Bao ; 63(3): 281-5, 2011 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-21681348

RESUMO

The aim of this study was to observe the electrophysiological characteristics of the isolated rat muscle spindle. The muscle spindle was isolated from rat soleus and the afferent discharge of the isolated muscle spindle was recorded by air-gap technique. In the basic physiological salt solution, the spontaneous impulses of muscle spindle were at a lower level with irregular intervals. The mean frequency of afferents was (51.78 ± 25.63) impulses/1 000 s (n = 13). The muscle spindle afferents were significantly increased and maintained over time by the addition of certain amino acids during the observation. The number of the action potential recorded per 1 000 s was 200-1 000 [mean: (687.62 ± 312.56) impulses/1 000 s, n = 17]. In addition to the typical propagated action potential, a large number of abortive spikes were observed. The results indicate that the activities of isolated muscle spindles in rats can be well maintained by the addition of certain amino acids. The results initially establish and provide the possibility for further research conducted in isolated rat muscle spindles.


Assuntos
Potenciais de Ação/fisiologia , Fusos Musculares/fisiologia , Músculo Esquelético/fisiologia , Aminoácidos/farmacologia , Animais , Fenômenos Eletrofisiológicos , Feminino , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio/farmacologia
12.
Sheng Li Xue Bao ; 63(1): 75-80, 2011 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-21340438

RESUMO

The present study aimed to study the changes of neurotrophin-3 (NT-3) expression of intrafusal muscle fibers in rat soleus muscles under simulated weightlessness. The tail-suspension (SUS) rat model was used to simulate weightlessness. Forty mature female Sprague-Dawley rats were randomly assigned to ambulatory control (CON), 3-day SUS, 7-day SUS, 14-day SUS and 21-day SUS groups. Immunohistochemistry ABC staining method and enzyme linked immunosorbent assay (ELISA) were used to detect the NT-3 expression of intrafusal muscle fibers in rat soleus muscles. The results from the immunohistochemistry staining technique showed that the extrafusal muscle fibers did not exhibit the NT-3-like immunoreactivity, and NT-3-like immunoreactivity was mainly expressed in nuclear bag 1 and nuclear bag 2 fibers of the muscle spindles. The ELISA results showed that the expression quantity of NT-3 in rat soleus muscles in control, 3-day SUS, 7-day SUS, 14-day SUS and 21-day SUS groups were (14.23±1.65), (14.11±1.53), (13.09±1.47), (12.45±1.51) and (9.85±1.52) pg/mg of tissue respectively. Compared to the control group, the expression quantity of NT-3 was significantly decreased after 14 days of SUS (P<0.05). After 21 days of SUS, the NT-3 expression was further reduced (P<0.01). These results suggest that simulated weightlessness induces an obvious decrease in the NT-3 expression level of intrafusal fibers in rat soleus muscles. Accompanying the simulated weightlessness extension, NT-3 expression in rat soleus muscle spindles is progressively decreased. These changes may contribute to the proprioceptive adaptations to microgravity.


Assuntos
Fusos Musculares/metabolismo , Músculo Esquelético/metabolismo , Neurotrofina 3/metabolismo , Simulação de Ausência de Peso , Animais , Regulação para Baixo , Feminino , Elevação dos Membros Posteriores , Neurotrofina 3/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
13.
J Muscle Res Cell Motil ; 31(3): 155-61, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20661631

RESUMO

During hind limb unloading (HU), the soleus is often in a shortened position and the natural physiological stimulus of muscle spindles is altered, such that muscle spindle activity also changes. Using isolated spindle conditions, the present study investigates the electrophysiological activity and ultrastructure of muscle spindles following HU. Results show that muscle spindle discharges fall into either of two main patterns, single spikes or spike clusters in shortened positions, with a steady frequency of 18-38 spikes/s (mean 29.08 +/- 2.45) in an extended position. Following 14-day HU, afferent discharge activity was significantly altered in soleus muscle spindles. Duration of individual spikes was significantly prolonged, from 0.54 +/- 0.05 ms for control rats to 1.53 +/- 0.25 ms for rats in the HU group. In a shortened position, regular rhythm afferent discharges were obviously depressed, and the majority of muscle spindles became silent, while in an extended position, the discharges remained continuous but with decreased frequency. Results also show that the ultrastructure of muscle spindles experience degenerative changes during HU. Altered muscle spindle afference could possibly modify the activity of motor neurons and further affect the activity of extrafusal fibers.


Assuntos
Elevação dos Membros Posteriores/efeitos adversos , Membro Posterior/fisiopatologia , Potenciais da Membrana , Fusos Musculares/fisiopatologia , Animais , Feminino , Membro Posterior/ultraestrutura , Fusos Musculares/ultraestrutura , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
14.
Neurosci Lett ; 448(3): 255-9, 2008 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-18950683

RESUMO

The present study investigates changes in red nucleus (RN) neuronal activity and the role of glutamate receptors (GluRs) after simulated microgravity (tail-suspension) in the rat using single-unit recording and microinjection. The results showed that tail-suspension for 3, 7, and 14 days could induce a significant decrease in spontaneous firing rate of RN neurons in a time-dependent manner. Unilateral microinjection of glutamate into the RN significantly increased the firing rate of RN neurons, but the increased firing rate was significantly reduced following tail-suspension time. Microinjection of the NMDA receptor antagonist MK-801 or the non-NMDA receptor antagonist DNQX into the RN blocked this excitatory effect induced by glutamate. However, microinjection of the metabotropic glutamate receptor (mGluR) antagonist (+/-)-MCPG into the RN had no effect. These results suggest that simulated microgravity can reduce excitability of RN neurons following a functional impairment of glutamate receptors. NMDA and non-NMDA receptors, but not mGluRs, are involved in the mediation of glutamate-evoked excitation of RN neurons. The decrease in excitability of RN neurons may be involved in simulated microgravity-induced muscle atrophy.


Assuntos
Ácido Glutâmico/farmacologia , Neurônios/efeitos dos fármacos , Receptores de Glutamato/fisiologia , Núcleo Rubro/efeitos dos fármacos , Simulação de Ausência de Peso , Animais , Maleato de Dizocilpina/farmacologia , Eletrofisiologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Glicina/análogos & derivados , Glicina/farmacologia , Elevação dos Membros Posteriores , Microinjeções , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato/efeitos dos fármacos , Núcleo Rubro/citologia , Estimulação Química
15.
Neurosci Lett ; 439(1): 1-6, 2008 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-18511191

RESUMO

To determine whether the neuronal activity of the spindle cord in muscle spindle afferent pathways is altered after a period of hindlimb unloading (Hu), and after recovery, we focused on c-Fos-immunoreactivity in the spinal cord evoked by excitation of the muscle spindle in normal gravity and after 3, 7, and 14 days of Hu, and after 14 days of Hu with an additional 2, 5, and 9 days of unrestricted cage activity. High frequency sinusoidal vibration (HFV) applied to the Achilles tendon was used for activation of the muscle spindle. Results showed that c-Fos-immunoreactive neurons evoked by HFV were mainly concentrated in lamina IV-VII of the ipsilateral spinal cord. After 14 days of Hu, the total number of labeled neurons in the spinal cord was significantly increased (P<0.05). The number of c-Fos-immunoreactive neurons in lamina IV and VI-VII were also significantly higher than that in normal rats (P<0.05). After 9 days of reloading, the total number of c-Fos-immunoreactive neurons and the pattern of their lamellar distribution were both recovered to pre-experimental levels. Our findings suggest that simulated weightlessness induces a large increase in neuronal excitation of the spinal cord in muscle spindle afferent pathways. Weight bearing immediately after Hu could induce completed recovery of excitability of the spinal cord in muscle spindle afferent pathways.


Assuntos
Expressão Gênica/fisiologia , Elevação dos Membros Posteriores/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Medula Espinal/metabolismo , Tendões/inervação , Vibração , Animais , Feminino , Estimulação Física/métodos , Ratos , Ratos Sprague-Dawley , Medula Espinal/anatomia & histologia , Fatores de Tempo
16.
Zhonghua Nan Ke Xue ; 14(2): 184-8, 2008 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-18390186

RESUMO

OBJECTIVE: To investigate the protective action of Epimedium against chemotherapy-induced damage to rat epididymides. METHODS: Fifty 60-day-old male rats were divided into a control, a model and a treatment group. Procarbazine was injected into the abdominal cavity of the model rats at the dose of 30 mg/(kg x d). In addition to procarbazine, Epimedium was given intragastrically to the treatment group. The changes in the ultrastructure of the epididymis were observed after 10 and 20 days. RESULTS: Electron microscopy showed that the chemotherapy-induced damages to the epididymal epithelia mainly included cell swelling, local cavitation of mitochondria, tumor-like change in nucleoli, agglutination of marginal translocation of heterochromatin and cell apoptosis. The damage to the epithelial ultrastructure was slight in the treatment group as compared with the model rats. Chemotherapy significantly affected sperm concentration, sperm viability and sialic acid (SA), which were (15.59 +/- 4.01) x 10(6)/ml, (76.71 +/- 10.11)% and (19.38 +/- 9.34) g/mg prot in the model group in comparison with (10.63 +/- 3.82) x 10(6)/ml (P < 0.01), (60.03 +/- 7.54)% (P < 0.01) and (13.62 +/- 7.81) g/g prot (P < 0.05) in the control. Epimedium significantly increased sperm viability in the treatment group (60.03 +/- 7.54)% as compared with the model rats (69.90 +/- 12.58)% (P < 0.05). CONCLUSION: Epimedium can lessen chemotherapy-induced damage to the epididymis and protect the reproductive function of rats.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Epididimo/efeitos dos fármacos , Epimedium/química , Animais , Antineoplásicos/toxicidade , Epididimo/fisiopatologia , Epididimo/ultraestrutura , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/prevenção & controle , Masculino , Microscopia Eletrônica de Transmissão , Fitoterapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
17.
Space Med Med Eng (Beijing) ; 18(4): 259-61, 2005 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-16224847

RESUMO

OBJECTIVE: To study the effects of 100 Hz vibration on ultrastructure of intrafusal and extrafusal fibers in soleus muscle of tail-suspended rats. METHOD: Weightlessness was simulated by tail suspension of female rats. The ultrastructure of intrafusal and extrafusal fibers of soleus muscle were examined after exposure to 100 Hz vibration. RESULT: The ultrastructure of intrafusal and extrafusal fibers of soleus muscles showed obvious retrograde changes after 7 d tail suspension, whereas these changes were not obvious after 7 d tail suspension plus 100 Hz vibration. CONCLUSION: High frequency vibration can counteract the effect of simulated weightlessness on ultrastructure of intrafusal and extrafusal fibers in soleus muscles of rats.


Assuntos
Músculo Esquelético/ultraestrutura , Vibração , Contramedidas de Ausência de Peso , Simulação de Ausência de Peso , Animais , Feminino , Elevação dos Membros Posteriores , Fibras Musculares de Contração Rápida/ultraestrutura , Ratos , Ratos Sprague-Dawley
18.
Space Med Med Eng (Beijing) ; 18(4): 262-6, 2005 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-16224848

RESUMO

OBJECTIVE: To study the effects of Ligustrazine (Lig) and Radix Astragali (Rad) on activities of myosin adenosine triphosphatase (mATPase) of soleus muscle and atrophy in tail-suspended rat. METHOD: Weightlessness was simulated by tail suspension in female rats. The activities of mATPase of intrafusal and extrafusal fibres in soleus muscle were detected by method of Ca2(+)-ATPase. RESULT: 1) Compared with tail-suspended (TS) group, the percentage of type II fibres of SOL in both Ligustrazine (Lig) group and Rad group decreased distinctly. Furthermore, the percentage of type I and type II fibres of SOL in Rad group showed no difference with control (CON) group. 2) The type I CSA of Lig group was markedly larger than that in TS group, and there was no difference as compared with that of CON group. CSA of type I, II and average CSA of Rad group were remarkably larger than those in TS group, and there were no difference as compared with those of CON group. 3) mATPase activities of intrafusal fibres in both Lig group and Rad group were approximate to that of CON group. CONCLUSION: Lig and Rad are both able to effectively prevent muscle atrophy caused by tail suspension, restrain the slow-twitch muscle transform to fast-twitch muscle and control the increase of mATPase activities caused by weightlessness.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Pirazinas/farmacologia , Simulação de Ausência de Peso , Animais , Feminino , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Miosinas/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
19.
Space Med Med Eng (Beijing) ; 17(3): 166-70, 2004 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15920840

RESUMO

OBJECTIVE: To study the effects of high frequency vibration on expression of myosin heavy chain (MHC) in intrafusal and extrafusal fibers in soleus muscles of tail-suspended rats. METHOD: Weightlessness was simulated by tail suspension of female rats. Using immunohistochemistry technique, changes of expression of MHC in intrafusal and extrafusal fibers of soleus muscles were detected. RESULT: Expression of fast MHC in intrafusal and extrafusal fibers of soleus muscles increased during 7 d of simulated weightlessness, whereas during 7 d of tail suspension plus high frequency vibration, these changes were not detected. CONCLUSION: High frequency vibration can counteract the changes in expression of MHC in intrafusal and extrafusal fibers of rats soleus under muscles of rats in simulated weightlessness situation.


Assuntos
Fibras Musculares de Contração Rápida/metabolismo , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Vibração , Simulação de Ausência de Peso , Animais , Feminino , Elevação dos Membros Posteriores , Imuno-Histoquímica , Ratos , Ratos Sprague-Dawley
20.
Space Med Med Eng (Beijing) ; 17(5): 340-4, 2004 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-15926231

RESUMO

OBJECTIVE: To study influence of 100 Hz sinusoidal vibration on muscle spindle afferents discharges of rat soleus muscles in simulated-weightlessness situation. METHOD: The tail-suspended rat model was used to simulate weightlessness, and 100 Hz sinusoidal vibration was performed by a vibrator. Unit activity was recorded electrophysiologically from the centrally cut filaments of the spinal dorsal roots innervating muscle spindles of the rat soleus muscle; then observation on the changes in afferent discharges from muscle spindle in a rat soleus muscles were made after 7 d. RESULT: 1) Compared with control muscle spindle afferents discharges of rat soleus muscles decreased after 7 d tail-suspension (P<0.05). 2) Compared with suspension the afferent discharges from soleus muscle spindles increased after 7 d tail-suspension with 100 Hz sinusoidal vibration. CONCLUSION: Sinusoidal vibration (100 Hz; 300 micrometers) can selectively activate muscle spindles. Muscle spindle afferent input of the suspended rats increased after the application of 7 d 100 Hz sinusoidal vibration.


Assuntos
Fusos Musculares/fisiologia , Músculo Esquelético/fisiologia , Vibração , Simulação de Ausência de Peso , Vias Aferentes/fisiologia , Animais , Elevação dos Membros Posteriores , Neurônios Aferentes/fisiologia , Ratos , Ratos Sprague-Dawley
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