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1.
Biochem Biophys Res Commun ; 506(4): 826-832, 2018 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-30389137

RESUMO

Voltage-gated sodium channels play important roles in human physiology. However, their complexity hinders the understanding of their physiology and pathology at atomic level. We took advantage of the structural reports of similar channels obtained by cryo-EM (EeNav1.4, and NavPaS), and constructed models of human Nav1.4 channels at closed and open states. The open-state model is very similar to the recently published cryo-EM structure of hNav1.4. The comparison of both models shows shifts of the voltage sensors (VS) of DIII and DIV. The activated position of VS-DII in the closed model was demonstrated by Ts1 docking, thereby confirming the requirement that VS-DI, VS-DII and VS-DIII must be activated for the channel to open. The interactions observed with VS-DIII suggest a stepwise, yet fast, transition from resting to activated state. These models provide structural insights on the closed-open transition of the channel.


Assuntos
Ativação do Canal Iônico , Modelos Biológicos , Músculo Esquelético/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.4/química , Canal de Sódio Disparado por Voltagem NAV1.4/metabolismo , Humanos , Simulação de Acoplamento Molecular
3.
Arq Bras Cardiol ; 109(3 Supl 1): 1-104, 2017.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29044300
4.
Arq. bras. cardiol ; 109(3,supl.1): 1-104, Sept. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-887936
5.
Br J Clin Pharmacol ; 70(5): 664-73, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21039760

RESUMO

AIMS: This study was conducted to determine whether atenolol was able to decrease BP level and mitigate BP increase during dynamic resistance exercise performed at three different intensities in hypertensives. METHODS: Ten essential hypertensives (systolic/diastolic BP between 140/90 and 160/105mmHg) were blindly studied after 6 weeks of placebo and atenolol. In each phase, volunteers executed, in a random order, three protocols of knee-extension exercises to fatigue: (i) one set at 100% of 1RM; (ii) three sets at 80% of 1RM; and (iii) three sets at 40% of 1RM. Intra-arterial radial blood pressure was measured throughout the protocols. RESULTS: Atenolol decreased systolic BP maximum values achieved during the three exercise protocols (100% = 186 ± 4 vs. 215 ± 7, 80% = 224 ± 7 vs. 247 ± 9 and 40% = 223 ± 7 vs. 252 ± 16mmHg, P < 0.05). Atenolol also mitigated an increase in systolic BP in the first set of exercises (100% =+38 ± 5 vs.+54 ± 9; 80% =+68 ± 11 vs. +84 ± 13 and 40% =+69 ± 7 vs.+84 ± 14, mmHg, P < 0.05). Atenolol decreased diastolic BP values and mitigated its increase during exercise performed at 100% of 1RM (126 ± 6 vs. 145 ± 6 and +41 ± 6 vs.+52 ± 6, mmHg, P < 0.05), but not at the other exercise intensities. CONCLUSIONS: Atenolol was effective in both reducing systolic BP maximum values and mitigating BP increase during resistance exercise performed at different intensities in hypertensive subjects.


Assuntos
Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Exercício/fisiologia , Hipertensão/tratamento farmacológico , Adulto , Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Treinamento de Resistência/métodos
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