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1.
Con-ciencia (La Paz) ; 8(2): 21-34, 2020. ilus.
Artigo em Inglês | LIBOCS, LILACS | ID: biblio-1147979

RESUMO

INTRODUCCIÓN: el canal de Potasio sensible a ATP (canal KATP) regula la producción de Insulina por células ß pancreáticas. La Glibenclamida (GBM) (fármaco antidiabético) y el ATP actúan como inhibidores de este canal, mientras que el ADP lo activa. El canal KATP es un octámero constituido por 4 subunidades centrales Kir6.2 que forman el poro y 4 subunidades externas de regulación SUR1. OBJETIVO: determinar la dinámica estructural entre las conformaciones abierta y cerrada del canal KATP en células pancreáticas. MÉTODO: análisis estructural comparativo de diferentes estructuras cristalográficas del canal KATP de células pancreáticas humanas empleando el software Chimera v1.11.2 RESULTADOS: La subunidad Kir6.2 presenta un dominio de unión a PIP2 (activador), una Hélice Interfacial (IFH) y un dominio N-terminal (KNtp). Por otro lado, la subunidad SUR1 que contiene el sitio de unión a la GBM, tiene 2 Dominios de Unión a Nucleótidos (NBD1/2), un bucle M5-Lh1 y un Motivo de Lazo formado por la interface entre el Dominio Trans-membrana 0 y el Bucle 0 (TMD0-L0). Los resultados del análisis dinámico estructural mediante herramientas bioinformáticas, indican que estas regiones participan activamente en los cambios conformacionales que dan lugar al cierre (inhibición) o apertura (activación) de este canal. CONCLUSIÓN: El estudio de la dinámica de activación e inhibición de los canales KATP es imprescindible para la evaluación, descubrimiento y/o diseño de nuevos compuestos naturales, que como la GBM, puedan promover la secreción de Insulina para coadyuvar o mejorar el tratamiento de pacientes diabéticos.


INTRODUCTION: the ATP-sensitive Potassium channel (KATP channel) regulates insulin production by pancreatic ß cells. Glibenclamide (GBM) (antidiabetic drug) and ATP act as inhibitors of this channel, while ADP activates it. The KATP channel is an octamer consisting of 4 central Kir6.2 subunits that form the pore and 4 external regulation subunits SUR1. OBJECTIVE: to determine the structural dynamics between the open and closed conformations of the KATP channel in pancreatic cells. METHOD: comparative structural analysis of different crystallographic structures of the KATP channel of human pancreatic cells using Chimera v1.11.2. RESULTS: the Kir6.2 subunit has a PIP2 binding domain (activator), an Interfacial Helix (IFH) and an N-terminal domain (KNtp). On the other hand, the SUR1 subunit that contains the GBM binding site, has 2 Nucleotide Binding Domains (NBD1/2), an M5-Lh1 loop and a Lasso Motif formed by the interface between the Trans-membrane Domain 0 and Loop 0 (TMD0-L0). The results of the dynamic structural analysis using bioinformatics tools indicate that these regions participate actively in the conformational changes that lead to the closure (inhibition) or opening (activation) of this channel. CONCLUSION: the study of the dynamics of activation and inhibition of the KATP channels is essential for the evaluation, discovery and/or design of new natural compounds, which like GBM, can promote insulin secretion to aid or improve the treatment of diabetic patients.


Assuntos
Humanos , Software , Canais de Potássio , Difosfato de Adenosina , Pacientes , Insulina
2.
J. venom. anim. toxins incl. trop. dis ; 25: e148118, 2019. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1002497

RESUMO

Scorpion venoms are natural sources of molecules that have, in addition to their toxic function, potential therapeutic applications. In this source the neurotoxins can be found especially those that act on potassium channels. Potassium channels are responsible for maintaining the membrane potential in the excitable cells, especially the voltage-dependent potassium channels (Kv), including Kv1.3 channels. These channels (Kv1.3) are expressed by various types of tissues and cells, being part of several physiological processes. However, the major studies of Kv1.3 are performed on T cells due its importance on autoimmune diseases. Scorpion toxins capable of acting on potassium channels (KTx), mainly on Kv1.3 channels, have gained a prominent role for their possible ability to control inflammatory autoimmune diseases. Some of these toxins have already left bench trials and are being evaluated in clinical trials, presenting great therapeutic potential. Thus, scorpion toxins are important natural molecules that should not be overlooked in the treatment of autoimmune and other diseases.(AU)


Assuntos
Animais , Venenos de Escorpião/toxicidade , Canais de Potássio , Terapia de Imunossupressão/métodos
3.
J. appl. oral sci ; 26: e20180048, 2018. graf
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-954519

RESUMO

Abstract Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Material and methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.


Assuntos
Animais , Masculino , Periodontite/fisiopatologia , Periodontite/metabolismo , Vasodilatação/fisiologia , Canais de Potássio/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Óxido Nítrico/metabolismo , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Proteína C-Reativa/análise , Nitroprussiato/farmacologia , Canais de Potássio/efeitos dos fármacos , Acetilcolina/farmacologia , Distribuição Aleatória , Perda do Osso Alveolar/fisiopatologia , Perda do Osso Alveolar/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Ratos Wistar , Peroxidase/análise , NG-Nitroarginina Metil Éster/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Ligadura
4.
Braz. j. med. biol. res ; 50(9): e5765, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-888990

RESUMO

Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.


Assuntos
Animais , Masculino , Ratos , Anfetaminas/farmacologia , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Vasodilatação , Vasodilatadores/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Ratos Wistar
5.
Arq. bras. cardiol ; 107(3): 223-229, Sept. 2016. graf
Artigo em Inglês | LILACS | ID: lil-796033

RESUMO

Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.


Resumo Fundamentos: Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Objetivos: Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Métodos: Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Resultados: Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina também foi prejudicada pelo tratamento prévio com EHJ. A inibição da Ca2+ATPase do reticulo sarcoplasmático não alterou o relaxamento pelo EHJ. Além disso, o EHJ inibiu a contração causada pelo influxo de Ca2+ estimulado por fenilefrina e KCl (75 mM). Conclusão: O EHJ induz vasodilatação independente do endotélio. Ativação dos canais de K+ e inibição do influxo de Ca2+ através da membrana estão envolvidas no efeito relaxante do EHJ.


Assuntos
Animais , Masculino , Vasodilatadores/farmacologia , Extratos Vegetais/farmacologia , Myrtaceae/química , Músculo Liso Vascular/efeitos dos fármacos , Aorta Torácica/efeitos dos fármacos , Fatores de Tempo , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Verapamil/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Reprodutibilidade dos Testes , Ratos Wistar , Bloqueadores dos Canais de Potássio/farmacologia
6.
Int. braz. j. urol ; 41(6): 1116-1125, Nov.-Dec. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-769752

RESUMO

Purpose: Sodium thiosulfate (STS) is clinically reported to be a promising drug in preventing nephrolithiasis. However, its mechanism of action remains unclear. In the present study, we investigated the role of mitochondrial KATP channel in the renal protection mediated by STS. Materials and Methods: Nephrolithiasis was induced in Wistar rats by administrating 0.4% ethylene glycol (EG) along with 1% ammonium chloride for one week in drinking water followed by only 0.75% EG for two weeks. Treatment groups received STS, mitochondrial KATP channel opener and closer exclusively or in combination with STS for two weeks. Results: Animals treated with STS showed normal renal tissue architecture, supported by near normal serum creatinine, urea and ALP activity. Diazoxide (mitochondria KATP channel opening) treatment to the animal also showed normal renal tissue histology and improved serum chemistry. However, an opposite result was shown by glibenclamide (mitochondria KATP channel closer) treated rats. STS administered along with diazoxide negated the renal protection rendered by diazoxide alone, while it imparted protection to the glibenclamide treated rats, formulating a mitochondria modulated STS action. Conclusion: The present study confirmed that STS render renal protection not only through chelation and antioxidant effect but also by modulating the mitochondrial KATP channel for preventing urolithiasis.


Assuntos
Animais , Masculino , Antioxidantes/farmacocinética , Quelantes/farmacologia , Etilenoglicol , Nefrolitíase/prevenção & controle , Canais de Potássio/farmacologia , Tiossulfatos/farmacologia , Antioxidantes/uso terapêutico , Oxalato de Cálcio/metabolismo , Quelantes/uso terapêutico , Modelos Animais de Doenças , Eletroforese em Gel de Ágar , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Nefrolitíase/patologia , Canais de Potássio/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Resultado do Tratamento , Tiossulfatos/uso terapêutico
7.
Braz. j. med. biol. res ; 48(6): 537-544, 06/2015. graf
Artigo em Inglês | LILACS | ID: lil-748218

RESUMO

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.


Assuntos
Animais , Masculino , Acetilcolina/farmacologia , Aorta Torácica/efeitos dos fármacos , Depressores do Apetite/farmacologia , Dietilpropiona/farmacologia , Vasodilatadores/farmacologia , Aorta Torácica/metabolismo , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Endotélio Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Fenilefrina/farmacologia , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Ratos Wistar , Tetraetilamônio/metabolismo , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos
8.
Braz. j. med. biol. res ; 48(6): 528-536, 06/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-748220

RESUMO

This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.


Assuntos
Animais , Masculino , Precondicionamento Isquêmico Miocárdico/métodos , Éteres Metílicos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/farmacologia , Canais de Potássio/farmacologia , Proteína Quinase C/farmacologia , Antiarrítmicos/farmacologia , Western Blotting , /análise , Ácidos Decanoicos/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hidroxiácidos/farmacologia , Isquemia/prevenção & controle , Substâncias Protetoras/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de Tempo , Troponina I/análise
9.
J. bras. nefrol ; 36(4): 512-518, Oct-Dec/2014. tab
Artigo em Inglês | LILACS | ID: lil-731151

RESUMO

Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .


Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .


Assuntos
Animais , Feminino , Masculino , Camundongos , Locus Cerúleo/efeitos dos fármacos , Entorpecentes/farmacologia , Inibição Neural/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Canais de Potássio/metabolismo , Bário/farmacologia , Cálcio/metabolismo , Encefalina Metionina/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G , Proteínas de Ligação ao GTP/metabolismo , Heterozigoto , Homozigoto , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Locus Cerúleo/citologia , Locus Cerúleo/fisiologia , Camundongos Knockout , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Subunidades Proteicas , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores , Canais de Potássio Corretores do Fluxo de Internalização/deficiência , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Canais de Potássio/deficiência , Canais de Potássio/genética
10.
Int. braz. j. urol ; 38(5): 687-694, Sept.-Oct. 2012. ilus
Artigo em Inglês | LILACS | ID: lil-655997

RESUMO

PURPOSE: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH3)4(caffeine)(NO)]C13 (Rut-Caf) and sodium nitroprusside (SNP). MATERIALS AND METHODS: The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE) (1 µM) and then concentration-response curves (10-12 - 10-4 M) were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM), oxyhemoglobin (10 µM), L-cysteine (100 µM), hydroxicobalamine (100 µM), glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50) and maximum effect (Emax). The substances showed activity through activation of the soluble guanylyl cyclase (sGC), because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09). There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.


Assuntos
Animais , Masculino , Coelhos , Relaxamento Muscular/fisiologia , Músculo Liso/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Compostos de Rutênio/farmacologia , GMP Cíclico/biossíntese , GMP Cíclico/química , Cisteína/farmacologia , Guanosina Monofosfato/biossíntese , Guanosina Monofosfato/química , Músculo Liso/fisiologia , Doadores de Óxido Nítrico/química , Nitroprussiato/química , Canais de Potássio/química , Compostos de Rutênio/química , Fatores de Tempo
11.
Braz. j. med. biol. res ; 45(3): 205-211, Mar. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-618049

RESUMO

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.


Assuntos
Animais , Ratos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Trimetazidina/farmacologia , Vasodilatadores/farmacologia , Ácidos Graxos/sangue , Glucose/análise , Miócitos Cardíacos/metabolismo , Canais de Potássio/metabolismo , Ratos Sprague-Dawley , Estreptozocina
12.
Rev. bras. cardiol. (Impr.) ; 24(1): 42-51, jan.-fev. 2011. ilus, tab
Artigo em Português | LILACS | ID: lil-591086

RESUMO

Intervalo QT é um parâmetro mensurado pelo eletrocardiograma de superfície que corresponde ao período que vai desde o início da despolarização até o final da repolarização ventricular. Devido à dependência da frequência cardíaca instantânea, o intervalo QT é corrigido pela frequência cardíaca. O intervalo QT corrigido é então empregado na prática clínica, por meio de valores de normalidade. Valores superiores aos recomendados pela literatura revelam o prolongamento significativo do intervalo QT - a síndrome do QT longo - uma desordem da condução elétrica do miocárdio que altera a repolarização ventricular e, consequentemente, aumenta a vulnerabilidade para o desenvolvimento de taquiarritmias ventriculares do tipo torsades de pointes e morte súbita. Esta síndrome pode apresentar origem congênita ou adquirida, com alterações nas propriedades dos canais iônicos de potássio, seja na sua cinética de ativação e inativação seja na densidade da corrente iônica ou mesmo em sua estrutura, resultando no prolongamento do tempo de repolarização ventricular. Assim, o objetivo deste trabalho foi revisar a literatura quanto à descrição ou à caracterização eletrofisiológica dos canais de potássio, em condições normais e relacionadas à síndrome do QT longo.


Assuntos
Humanos , Arritmias Cardíacas/diagnóstico , Função Ventricular/fisiologia , Canais de Potássio , Síndrome do QT Longo/complicações , Síndrome do QT Longo/diagnóstico , Ventrículos do Coração/fisiopatologia , Morte Súbita , Técnicas Eletrofisiológicas Cardíacas/métodos , Técnicas Eletrofisiológicas Cardíacas
13.
Clinics ; 66(2): 321-325, 2011. graf
Artigo em Inglês | LILACS | ID: lil-581521

RESUMO

OBJECTIVES: The purpose of this work was to determine whether the intraperitoneal administration of glibenclamide as a K ATP channel blocker could have an effect on the antinociceptive effects of antidepressants with different mechanisms of action. METHODS: Three antidepressant drugs, amitriptyline as a dual-action, nonselective inhibitor of noradrenaline and a serotonin reuptake inhibitor, fluvoxamine as a selective serotonin reuptake inhibitor and maprotiline as a selective noradrenaline reuptake inhibitor, were selected, and the effect of glibenclamide on their antinociceptive activities was assessed in male Swiss mice (25-30 g) using a formalin test. DISCUSSION: None of the drugs affected acute nociceptive responses during the first phase. Amitriptyline (5, 10 mg/ kg), maprotiline (10, 20 mg/kg) and fluvoxamine (20 and 30 mg/kg) effectively inhibited pain induction caused by the second phase of the formalin test. Glibenclamide (5 mg/kg) alone did not alter licking behaviors based on a comparison with the control group. However, the pretreatment of animals with glibenclamide (10 and 15 mg/kg) partially reversed the antinociceptive effects of fluvoxamine but not those of maprotiline. In addition, the highest dose of glibenclamide (15 mg/kg) partially prevented the analgesic effect of amitriptyline. CONCLUSION: Therefore, it seems that adenosine triphosphate-dependent potassium channels have a major role in the analgesic activity of amitriptyline and fluvoxamine.


Assuntos
Animais , Masculino , Camundongos , Analgésicos/uso terapêutico , Antidepressivos/uso terapêutico , Glibureto/farmacologia , Medição da Dor/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/efeitos dos fármacos , Análise de Variância , Amitriptilina/uso terapêutico , Interações Medicamentosas , Fluvoxamina/uso terapêutico , Modelos Animais , Maprotilina/uso terapêutico , Dor/induzido quimicamente , Dor/tratamento farmacológico , Distribuição Aleatória
14.
West Indian med. j ; 59(5): 473-478, Oct. 2010. tab
Artigo em Inglês | LILACS | ID: lil-672661

RESUMO

OBJECTIVE: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa. METHODS: Swiss albino mice of either gender weighing between 25-30 g were used for the study. The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests. RESULTS: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However, reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers. CONCLUSIONS: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However, such interaction occurs at the level of potassium channels rather than at the level of receptors.


OBJETIVO: El estudio fue realizado para evaluar el efecto de los abridores de canales de potasio en la tolerancia a la morfina, y viceversa. MÉTODOS: Para el estudio, se usaron ratones albinos suizos de ambos sexos que pesaban entre 25-30 g. El estudio evalúa el efecto de los abridores de canales de potasio (cromacalina, diazóxido y minoxidil) en la tolerancia a la morfina, y viceversa, usando la prueba de la sacudida de la cola y la prueba de la formalina. RESULTADOS: El efecto antinociceptivo de la cromacalina y el minoxidil fue significativamente reducido cuando se le administró a los ratones tolerantes a la morfina, en ambas pruebas conductuales. Sin embargo, se observó un efecto analgésico reducido de diazóxido sobre la tolerancia a la morfina en la prueba de la formalina, pero no en la prueba de la sacudida de la cola. Se observó tolerancia al administrar morfina a animales crónicamente tratados con cualquiera de los abridores de canales de potasio. El mismo efecto fue observado cuando se inyectó la morfina al grupo tratado con una combinación de morfina y cualquiera de los abridores de canales de potasio. CONCLUSIONES: Por consiguiente, este estudio sugiere que tanto la morfina como los abridores de canales de potasio son tolerantes cruzados. Sin embargo, tal interacción ocurre a nivel de los canales de potasio más bien que a nivel de los receptores.


Assuntos
Animais , Camundongos , Analgésicos Opioides/farmacologia , Cromakalim/farmacologia , Diazóxido/farmacologia , Tolerância a Medicamentos , Minoxidil/farmacologia , Morfina/farmacologia , Canais de Potássio/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Modelos Animais , Dor
15.
Braz. j. pharm. sci ; 45(3): 483-489, July-Sept. 2009. graf, ilus
Artigo em Inglês | LILACS | ID: lil-533176

RESUMO

The negative inotropic effect of aqueous fraction (AqF) obtained from the acetic extract of Psidium guajava L leaf was investigated on the guinea pig left atrium. Myocardial force was measured isometrically (27 ± 0.1 ºC, 2 Hz). AqF (100 μg/ml) reduced contractility of about 85 ± 9.4 percent (n = 4, p < 0.001, Fcalc = 51.70, F(0.01; 4; 21) = 5.09, EC50 = 14.28 ± 3 μg/mL) in a concentration-dependent fashion. This effect was reduced by 20 mM of tetraethylammonium (TEA), increasing EC50 to 50 ± 7 μg/ml (n = 4, p < 0.001, Fcalc = 282.13; F(0.01; 21; 66) = 2.36). AqF (100 μg/ml) shifted to the right the CaCl2 concentration-effect curve, increasing the EC50 from 2170 ± 112 to 2690 ± 132 μM (n = 3, p < 0.001, Fcalc = 220.80 ; F(0.01; 29; 60) = 2.19). L-NAME (100 μM) did not modify the AqF inotropic effect (n = 3, p > 0.05) sugesting that the oxide nitric pathway did not participate of the action mechanism of AqF. We can conclude that AqF depresses the atrial contractile by reducing the calcium entry in myocardial cells and also by openenig potassium channels of cardiac tissue.


O efeito inotrópico da fração aquosa (AqF) do extrato acético das folhas de Psidium guajava L. foi investigado em átrio esquerdo de cobaia. A força miocárdica foi medida isometricamente (27 ± 0,1 ºC; 2 Hz). A AqF (100 μg/mL) reduziu a contratilidade em até 85 ± 9,4 por cento (n = 4; p < 0,001; Fcalc = 51,70; F(0,01; 4; 21) = 5,09; CE50 = 14,28 ± 3 μg/mL) de forma dependente da concentração. Este efeito foi reduzido pelo tetraetilamônio (TEA, 20 mM) que também aumentou a CE50 de 14,28 ± 3 μg/mL para 50 ± 7 μg/mL (n = 4; p < 0,001; Fcalc = 282,13; F(0,01; 21; 66) = 2,36). A AqF (100 μg/mL) deslocou para a direita a curva concentração-efeito do CaCl2, aumentando a CE50 de 2170 ± 112 para 2690 ± 132 μM (n = 3; p < 0,001; Fcalc = 220,80 ; F(0,01; 29; 60) = 2,19). Por outro lado, o L-NAME (100 μM) não alterou o efeito inotrópico da AqF (n = 3; p > 0,05), sugerindo que a via do óxido nítrico não participa do mecanismo de ação da AqF. Conclui-se que a AqF deprime a contratilidade atrial por reduzir a entrada de cálcio nas células miocárdicas e por abrir canais de potássio deste tecido.


Assuntos
Animais , Cobaias , Canais de Cálcio , Átrios do Coração , Extratos Vegetais , Canais de Potássio , Psidium/química , Cardiotônicos , Estudos de Intervenção , Contração Miocárdica , Miocárdio , Miócitos Cardíacos
16.
Braz. j. med. biol. res ; 42(1): 87-93, Jan. 2009. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-505424

RESUMO

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.


Assuntos
Animais , Ratos , Proteínas Quinases Dependentes de GMP Cíclico/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Rutênio/farmacologia , Aorta/efeitos dos fármacos , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Hipertensão Renal/fisiopatologia , Relaxamento Muscular , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/fisiopatologia , Óxido Nítrico/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Rutênio/química , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
17.
Braz. j. biol ; 68(3): 571-575, Aug. 2008. graf, tab
Artigo em Inglês | LILACS | ID: lil-493576

RESUMO

The aim of this study was to describe the effect of hypoxia on whole body ion fluxes and hematological parameters in two Amazonian teleosts: Serrasalmus eigenmanni and Metynnis hypsauchen. The increase of Na+ and Cl- effluxes on M. hypsauchen exposed to hypoxia may be related to an increase of gill ventilation and effective respiratory surface area, to avoid a reduction in the oxygen uptake, and/or with the decrease of pHe, that could inhibit Na+ and Cl- transporters and, therefore, reduce influx of these ions. Effluxes of Na+ and Cl- were lower in hypoxia than in normoxia for S. eigenmanni, possibly because in hypoxia this species would reduce gill ventilation and oxygen uptake, which would lead to a decrease of gill ion efflux and, consequently, reducing ion loss. The increase on hematocrit (Ht) during hypoxia in M. hypsauchen probably was caused by an increase of the red blood cell volume (MCV). For S. eigenmanni the increase on glucose possibly results from the usage of glucose reserve mobilization. Metynnis hypsauchen showed to be more sensitive to hypoxia than Serrasalmus eigenmanni, since the first presented more significant alterations on these osmoregulatory and hematological parameters. Nevertheless, the alterations observed for both species are strategies adopted by fishes to preserve oxygen supply to metabolizing tissues during exposure to hypoxia.


O objetivo deste trabalho foi descrever o efeito da hipoxia no fluxo iônico corporal e nos parâmetros hematológicos em duas espécies de teleósteos da Amazônia: Serrasalmus eigenmanni e Metynnis hypsauchen. O aumento dos efluxos de Na+ e Cl- em M. hypsauchen expostos à hipoxia pode estar relacionado ao aumento da ventilação branquial e da eficiência da área da superfície respiratória, a fim de evitar redução na captação de oxigênio; e/ou com a diminuição do pHe, que pode inibir os transportadores de Na+ e Cl- e, então, reduzir o influxo destes íons. Os efluxos de Na+ e Cl- foram menores em hipoxia do que em normoxia para a espécie S. eigenmanni, possivelmente porque esta espécie em hipoxia poderia reduzir a ventilação branquial e a captação de oxigênio, a qual levaria a uma diminuição do efluxo branquial de íons e, conseqüentemente, à redução da perda de íons. O aumento do hematócrito (Ht) durante hipoxia em M. hypsauchen provavelmente foi causado pelo aumento do volume das células vermelhas do sangue (MCV). Para a espécie S. eigenmanni, o aumento da glicose possivelmente foi resultado do uso da mobilização da reserva de glicose. A espécie Metynnis hypsauchen mostrou ser mais sensível à hipoxia do que a espécie Serrasalmus eigenmanni, uma vez que a primeira espécie apresentou mais alterações significativas em seus parâmetros osmorregulatórios e hematológicos. Contudo, as alterações observadas em ambas as espécies são estratégias adotadas pelos peixes a fim de preservar o suprimento de oxigênio para metabolização nos tecidos durante exposição à hipoxia.


Assuntos
Animais , Hipóxia/metabolismo , Peixes/metabolismo , Canais de Potássio/metabolismo , Canais de Sódio/metabolismo , Adaptação Fisiológica , Hipóxia/sangue , Peixes/sangue , Rios
18.
Arq. bras. med. vet. zootec ; 59(6): 1516-1522, dez. 2007. ilus, tab
Artigo em Português | LILACS | ID: lil-476126

RESUMO

Dois estudos foram realizados com vacas lactantes utilizadas como unidade experimental e doadoras de líquido ruminal, sendo as populações de bactérias utilizadas para avaliar a ação de níveis crescentes de lasalocida e monensina na resistência à perda de potássio intracelular, e para produção de gases in vitro. A perda de potássio (Kmax) da lasalocida foi menor para a população de bactérias obtidas do líquido de rúmen de vacas submetidas a dietas com monensina, óleo de soja e monensina mais óleo de soja (19,4 a 25,4 por cento) quando comparada com a perda de potássio em vacas submetidas a dietas sem ionóforo e óleo de soja (30,1 por cento). O mesmo ocorreu para a perda de potássio da monensina, em que o menor valor foi de 6,5 por cento para monensina mais óleo e o maior, de 29,5 por cento, para o controle. Necessita-se de alta concentração de monensina (Kd= 2,3µM), porém baixa de lasalocida (Kd= 0,2µM) para causar a metade da perda máxima de potássio intracelular da população de bactérias do rúmen de vacas submetidas a dietas com monensina. As populações de bactérias de vacas submetidas às dietas com monensina foram sensíveis à lasalocida. As amostras incubadas com própolis produziram menor volume de gases (12,9ml/100g de MS)


Two studies were carried out with lactating cows as experimental units and ruminal fluid donors. The ruminal bacteria population was used to evaluate the action of increasing levels of lasalocid and monensin on resistance of intracellular potassium depletion and in vitro gas production intracellular depletion potassium (Kmax) of lasalocid was lower to ruminal bacteria population obtained from rumen of cows fed diets with monensin, soybean oil and monensin plus soybean oil (19.4 to 25.4 percent) when compared to cows fed with control diet (30.1 percent). The same occurred for intracellular depletion potassium (Kmax) of monensin, in which the lowest value was 6.5 percent to monensin plus soybean oil and the greatest was 29.5 percent to control. High monensin concentration (Kd= 2.3µM) and low lasalocid concentration (Kd= 0.2µM) were necessary to cause half of maximum potassium depletion in ruminal bacteria population from cows fed diet with monensin. The ruminal bacteria population from cows feed diet with monensin were sensible to lasalocid. In vitro gas production showed the lowest volume when diets were incubated with propolis (12,9ml/100g of DM)


Assuntos
Animais , Feminino , Bovinos , Canais de Potássio/farmacocinética , Flatulência/induzido quimicamente , Flatulência/veterinária , Ionóforos/administração & dosagem , Lasalocida/administração & dosagem , Lasalocida/farmacocinética , Monensin/administração & dosagem , Monensin/farmacocinética
19.
Acta biol. colomb ; 12(1): 87-98, jun. 2007. graf
Artigo em Inglês | LILACS | ID: lil-468992

RESUMO

Spermatozoa in Characid fish remain immobile in seminal plasma and are activated when freed into water where the ionic balance seems to be the main factor starting the activation process. This process was the target of the present study with emphasis on the activation of motility and on motility maintenance over time. The effect of isosmotic solutions was analyzed taking into account the possible combinations of the following ions, Ca2+, K+, Mg2+ and Na+ as well as the effect of channel blocking agents. The parameters measured were cells with motility (per cent), duration of motility (s), plasma membrane potential, and the effect of channel blockers on activation time and on motility. There was an increased motility when the semen was incubated in solutions containing K+ (p<0.05) compared with the control (CaNaMgK solution); the longest duration of motility was attained when the incubation was performed in solutions containing Na+ and Mg2+ (p<0.05). All solutions induced a change in membrane potential detected after 15 s of activation. Blocking K+, Ca2+ and Na+ channels did not alter motility but decreased the activation time (p<0.05). Potassium induced activation at all concentrations up to 105 mM, but motility was drastically decreased at concentrations higher than 140 mM (p<0.05). The conclusion is that interaction of the ionic environment with the cell membrane leads to changes in membrane potential and intracellular signalling that trigger sperm motility in Brycon henni.


Assuntos
Cálcio/antagonistas & inibidores , Canais de Cálcio/fisiologia , Canais de Potássio/fisiologia , Espermatozoides/química
20.
Rev. invest. clín ; 59(1): 57-72, ene.-feb. 2007. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-632392

RESUMO

Long QT Syndrome (LQTS) is a cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk to sudden death secondary to ventricular dysrrhythmias. Was the first cardiac channelopathy described and is probably the best understood. After a decade of the sentinel identification of ion channel mutation in LQTS, genotype-phenotype correlations have been developed along with important improvement in risk stratification and genetic guided-treatment. Genetic screening has shown that LQTS is more frequent than expected and interestingly, ethnic specific polymorphism conferring increased susceptibility to drug induced QT prolongation and torsades de pointes have been identified. A better understanding of ventricular arrhythmias as an adverse effect of ion channel binding drugs, allow the development of more safety formulas and better control of this public health problem. Progress in understanding the molecular basis of LQTS has been remarkable; eight different genes have been identified, however still 25% of patients remain genotype-negative. This article is an overview of the main LQTS knowledge developed during the last years.


El síndrome de QT largo (SQTL) es una canalopatía que genera grave alteración en la repolarización ventricular predispone a arritmias malignas y muerte súbita. Fue la primera canalopatía arritmogénica descrita y quizá la mejor entendida hasta ahora. Transcurrida ya más de una década de la identificación de la primera mutación asociada al SQTL, se ha hecho evidente que este trastorno es mucho más frecuente de lo que inicialmente se pensaba; los avances en el conocimiento de la fisiopatología molecular de esta enfermedad han permitido hacer una correlación genotipo-fenotipo, optimizando el tratamiento y permitiendo estratificar el riesgo en forma precisa. Se ha logrado entender con mayor detalle los efectos adversos de distintas drogas que interactúan con los canales iónicos, permitiendo así generar fármacos más seguros y, en su defecto, monitorizar de cerca aquellos que a pesar de tener este efecto adverso, es necesaria su administración. Los avances son importantes pero no todo está dicho, 25% de los casos no tienen mutaciones en los genes descritos hasta la fecha, por lo que el SQTL continúa siendo motivo de investigación. El presente artículo constituye un resumen de los principales conceptos desarrollados en los últimos diez años que han sido cruciales en el manejo de esta enfermedad.


Assuntos
Humanos , Síndrome do QT Longo , Bradicardia/diagnóstico , Bradicardia/embriologia , Bradicardia/genética , Fármacos Cardiovasculares/uso terapêutico , Morte Súbita Cardíaca/etiologia , Cardioversão Elétrica , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Coração Fetal/fisiopatologia , Ganglionectomia , Genótipo , Transporte de Íons/genética , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/classificação , Síndrome do QT Longo/complicações , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/embriologia , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/genética , Síndrome do QT Longo/terapia , Marca-Passo Artificial , Fenótipo , Diagnóstico Pré-Natal , Canais de Potássio/genética , Canais de Potássio/fisiologia , Canais de Sódio/genética , Canais de Sódio/fisiologia , Gânglio Estrelado/cirurgia , Taquicardia Ventricular/etiologia , Torsades de Pointes/etiologia
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