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1.
Mol Biol (Mosk) ; 58(1): 160-170, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38943588

RESUMO

CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, such as gene editing, regulation of gene transcription, modification of epigenome etc. While CRISPR/Cas systems proved to be highly effective for correcting genetic disorders and treating infectious diseases and cancers in experimental settings, clinical translation of these results is hampered by the lack of efficient CRISPR/Cas delivery vehicles. Modern synthetic nanovehicles based on organic and inorganic polymers have many disadvantages, including toxicity issues, the lack of targeted delivery, and complex and expensive production pipelines. In turn, exosomes are secreted biological nanoparticles that exhibit high biocompatibility, physico-chemical stability, and the ability to cross biological barriers. Early clinical trials found no toxicity associated with exosome injections. In the recent years, exosomes have been considered as perspective delivery vehicles for CRISPR/Cas systems in vivo. The aim of this study was to analyze the efficacy of CRISPR/Cas stochastic packaging into exosomes for several human cell lines. Here, we show that Cas9 protein is effectively localized into the compartment of intracellular exosome biogenesis, but stochastic packaging of Cas9 into exosomes turns to be very low (~1%). As such, stochastic packaging of Cas9 protein is very ineffective and cannot be used for gene editing purposes. Developing novel tools and technologies for loading CRISPR/Cas systems into exosomes is needed.


Assuntos
Sistemas CRISPR-Cas , Exossomos , Edição de Genes , Exossomos/metabolismo , Exossomos/genética , Humanos , Edição de Genes/métodos , Proteína 9 Associada à CRISPR/genética , Proteína 9 Associada à CRISPR/metabolismo
2.
Photosynth Res ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224422

RESUMO

C-phycocyanin (C-PC) is the main component of water-soluble light-harvesting complexes (phycobilisomes, PBS) of cyanobacteria. PBS are involved in the absorption of quantum energy and the transfer of electronic excitation energy to the photosystems. A specific environment of C-PC chromophoric groups is provided by the protein matrix structure including protein-protein contacts between different subunits. Registration of C-PC spectral characteristics and the fluorescence anisotropy decay have revealed a significant pH influence on the chromophore microenvironment: at pH 5.0, a chromophore is more significantly interacts with the solvent, whereas at pH 9.0 the chromophore microenvironment becomes more viscous. Conformations of chromophores and the C-PC protein matrix have been studied by Raman and infrared spectroscopy. A decrease in the medium pH results in changes in the secondary structure either the C-PC apoproteins and chromophores, the last one adopts a more folded conformation.

3.
Mol Biol (Mosk) ; 57(6): 1188-1198, 2023.
Artigo em Russo | MEDLINE | ID: mdl-38062968

RESUMO

Metabolic stress caused by a lack of glucose significantly affects the state of red blood cells, where glycolysis is the main pathway for the production of ATP. Hypoglycemia can be both physiological (occurring during fasting and heavy physical exertion) and pathological (accompanying a number of diseases, such as diabetes mellitus). In this study, we have characterized the state of isolated erythrocytes under metabolic stress caused by the absence of glucose. It was established that 24 h of incubation of the erythrocytes in a glucose-free medium to simulate blood plasma led to a two-fold decrease in the ATP level into them. The cell size, as well as intracellular sodium concentration increased. These findings could be the result of a disruption in ion transporter functioning because of a decrease in the ATP level. The calcium level remained unchanged. With a lack of glucose in the medium of isolated erythrocytes, there was no increase in ROS and a significant change in the level of nitric oxide, while the level of the main low-molecular weight thiol of cells, glutathione (GSH) decreased by almost 2 times. It was found that the metabolic stress of isolated red blood cells induced hemoglobin glutathionylation despite the absence of ROS growth. The cause was the lack of ATP, which led to a decrease in the level of GSH because of the inhibition of its synthesis and, probably, due to a decrease in the NADPH level required for glutathione (GSSG) reduction and protein deglutathionylation. Thus, erythrocyte metabolic stress induced hemoglobin glutathionylation, which is not associated with an increase in ROS. This may have an important physiological significance, since glutathionylation of hemoglobin changes its affinity for oxygen.


Assuntos
Glutationa , Hemoglobinas , Dissulfeto de Glutationa/análise , Dissulfeto de Glutationa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxirredução , Glutationa/análise , Glutationa/metabolismo , Hemoglobinas/análise , Hemoglobinas/metabolismo , Eritrócitos/química , Eritrócitos/metabolismo , Estresse Oxidativo , Glucose/análise , Glucose/metabolismo , Trifosfato de Adenosina
4.
Heliyon ; 7(9): e08088, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34632152

RESUMO

High-salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodelling, cardiac hypertrophy and stroke incidence. Alterations in NO production, inflammation and endothelial cell stiffening are considered now as plausible mediators of cardiovascular dysfunction. We studied early responses of endothelial cells (HUVEC) caused by a moderate increase in extracellular sodium concentration. Exposure of HUVEC to elevated sodium within the physiological range up to 24 h is accompanied by changes in monovalent cations fluxes and Na,K-ATPase activation, and, in turn, results in a significant decrease in the content of PTGS2, IL6 and IL1LR1 mRNAs. The expression of NOS3 and FOS genes, as well as the abundance of cytosolic and nuclear NFAT5 protein, remained unchanged. We assessed the mechanical properties of endothelial cells by estimating Young's modulus and equivalent elastic constant using atomic force and interference microscopy, respectively. These parameters were unaffected by elevated-salt exposure for 24 h. The data obtained suggest that even small and short-term elevations of extracellular sodium concentration affect the expression of genes involved in the control of endothelial function through the Na+ i/K+ i-dependent mechanism(s).

5.
Bull Exp Biol Med ; 168(3): 378-380, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31938921

RESUMO

Thermal stimulation of various parts of the skin in Hirudo medicinalis increases the frequency of spontaneous rhythmic excitation of Retzius neurons in leech ganglia. It was shown that the frequency of spontaneous rhythmic excitation of Retzius cells in the segmental ganglion increases only in response to thermal stimulation and returns to initial values upon cooling. This effect was also detected in neurons that are not directly connected by nerve fibers with the particular skin area. Changes in the frequency of spontaneous rhythmic excitation of Retzius cells in the segmental ganglion were observed during thermal stimulation of not only leech body, but also of the head and caudal suckers. These changes in spontaneous rhythmic excitation of Retzius cells in the segmental ganglion during thermal stimulation were observed in Hirudo medicinalis, but not in Macrobdella decora.


Assuntos
Cistos Glanglionares/metabolismo , Sanguessugas/citologia , Sanguessugas/metabolismo , Animais , Gânglios/metabolismo , Fibras Nervosas/metabolismo , Neurônios/metabolismo , Pele/citologia , Pele/metabolismo
6.
J Biol Phys ; 45(4): 367-377, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31758351

RESUMO

The intensity of erythrocyte membrane fluctuations was studied by laser interference microscopy (LIM), which provide information about mechanical properties of the erythrocyte membrane. Atomic force microscopy (AFM) was used to study erythrocyte surface relief; it is related to the cytoskeleton structure of erythrocyte membrane. Intact human erythrocytes and erythrocytes with a destroyed cytoskeleton were used. According to the obtained results, cytoskeleton damage induced by heating up to 50 °Ð¡ results in a reduced intensity of cell membrane fluctuations compared to non-treated cells (20.6 ± 10.2 vs. 30.5 ± 5.5 nm, correspondingly), while the roughness of the membrane increases (4.5 ± 1.5 vs. 3.4 ± 0.5 nm, correspondingly).


Assuntos
Citoesqueleto/metabolismo , Membrana Eritrocítica/metabolismo , Eritrócitos/citologia , Temperatura Alta/efeitos adversos , Fenômenos Mecânicos , Fenômenos Biomecânicos
7.
Biochemistry (Mosc) ; 84(11): 1280-1295, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760918

RESUMO

Maintenance of non-equilibrium Na+ and K+ distribution between cytoplasm and extracellular medium suggests existence of sensors responding with conformational transitions to the changes of these monovalent cations' intracellular concentration. Molecular nature of monovalent cation sensors has been established in Na,K-ATPase, G-protein-coupled receptors, and heat shock proteins structural studies. Recently, it was found that changes in Na+ and K+ intracellular concentration are the key factors in the transcription and translation control, respectively. In this review, we summarize results of these studies and discuss physiological and pathophysiological significance of Na+i,K+i-dependent gene expression regulation mechanism.


Assuntos
Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Sódio/metabolismo , Animais , Cátions Monovalentes/química , Citoplasma/metabolismo , Proteínas de Choque Térmico/metabolismo , Potássio/química , Biossíntese de Proteínas , Sódio/química , Transcrição Gênica
8.
Bull Exp Biol Med ; 166(3): 386-389, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627898

RESUMO

We demonstrated the possibility of penetration of magnetite-gold nanoparticles conjugated with prostate-specific membrane antigen into mouse macrophages. It was found that after 3-h incubation with nanoparticles in a concentration of 15 mg/liter at 37oC, they were seen in only 13% macrophages. In about 90% cells, the nanoparticles were detected within the cytoplasm. Under these conditions, membrane damage was revealed in 25% cells. These results should be taken into account in further development and application of nanomaterials for diagnostic and therapeutic purposes in oncology.


Assuntos
Antígenos de Superfície/metabolismo , Morte Celular/efeitos dos fármacos , Meios de Contraste/toxicidade , Glutamato Carboxipeptidase II/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Animais , Antígenos de Superfície/química , Carbocianinas/química , Linhagem Celular Tumoral , Meios de Contraste/química , Endocitose/fisiologia , Corantes Fluorescentes/química , Glutamato Carboxipeptidase II/química , Ouro/química , Humanos , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/ultraestrutura , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Cultura Primária de Células , Próstata/diagnóstico por imagem , Próstata/metabolismo , Próstata/patologia , Ligação Proteica
9.
J Mater Chem B ; 4(3): 539-546, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32263217

RESUMO

A great enhancement in Raman scattering (SERS) from heme-containing submembrane biomolecules inside intact erythrocytes and functional mitochondria is demonstrated for the first time using silver-silica beads prepared using a new method involving aerosol pyrolysis with aqueous diamminesilver(i) hydroxide as a unique source of plasmonic nanoparticles for SiO2 microspheres. The recorded SERS spectra reveal a set of characteristic peaks at 750, 1127, 1170, 1371, 1565, 1585 and 1638 cm-1, resulting from the normal group vibrations of the pyrrole rings, methine bridges and side radicals in the heme molecules. The SERS spectra of functional mitochondria are sensitive to the activity of the mitochondrial electron transport chain, thus making the method a novel label-free approach to monitor the redox state and conformation of cytochromes in their natural cell environment. The developed nanocomposites are highly suitable for the analysis of biological objects due to their robust synthesis and superior spatial and temporal signal reproducibility, which was preserved for a period of at least one year.

10.
Bull Exp Biol Med ; 159(2): 213-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26085354

RESUMO

Raman spectroscopy was used to investigate changes in hemoglobin conformation and its ability to transfer O2 and NO induced by activation of purinergic receptors of erythrocytes with extracellular ATP. It was found that addition of ATP in a final concentration of 0.1 mM and higher to erythrocyte suspension was followed by changes in hematoporphyrin conformation, while addition of ATP in a concentration of 1 mM and higher increased the proportion of oxyhemoglobin and NO-associated hemoglobin complexes. In case of purinergic receptors activation in blood erythrocytes, significant changes in hemoglobin conformation were observed only at a final ATP concentration of 5 mM, probably due to buffer properties of the blood.


Assuntos
Eritrócitos/metabolismo , Hemoglobinas/química , Receptores Purinérgicos/metabolismo , Trifosfato de Adenosina/farmacologia , Relação Dose-Resposta a Droga , Hematoporfirinas/química , Hemoglobinas/metabolismo , Humanos , Óxido Nítrico/metabolismo , Oxigênio/metabolismo , Conformação Proteica , Análise Espectral Raman
11.
Plant Physiol Biochem ; 81: 208-11, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24836446

RESUMO

In this paper the changes on growth, photosynthesis and water relations were tested by non-invasive fluorescence method. The applications of this method allow to determine some functional properties of prestigious maize inbred lines with erect top leaves. So the temperature dependency of delayed fluorescence intensity maximum of ZPPL 16 is observed at higher temperatures than for ZPPZ 62. This fact correlates with low values of phase transition of activation energy Ea in thylakoid membrane and accompanied by a decrease of the angle and area of the leaf, as well as with the content and the rate of water release from the seed. It seems reasonable to assume that, DF can be applied in breeding and maize hybrid seed production for the estimation of prestigious maize inbred lines and their resistance adaptability to increased and high temperatures, as well as, to drought.


Assuntos
Tilacoides/metabolismo , Água/metabolismo , Zea mays/metabolismo , Clorofila/metabolismo , Secas , Fluorescência , Endogamia , Fotossíntese , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Temperatura , Zea mays/crescimento & desenvolvimento
12.
Ageing Res Rev ; 16: 1-11, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24742502

RESUMO

The generation of ROS underlies all solar infrared-affected therapeutic and pathological cutaneous effects. The signaling pathway NF-kB is responsible for the induced therapeutic effects, while the AP-1 for the pathological effects. The different signaling pathways of infrared-induced ROS and infrared-induced heat shock ROS were shown to act independently multiplying the influence on each other by increasing the doses of irradiation and/or increasing the temperature. The molecular action mechanisms of solar infrared radiation and heat on human skin are summarized and discussed in detail in the present paper. The critical doses are determined. Protection strategies against infrared-induced skin damage are proposed.


Assuntos
Temperatura Alta/efeitos adversos , Raios Infravermelhos/efeitos adversos , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos da radiação , Animais , Antioxidantes/farmacologia , Humanos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Medição de Risco , Fatores de Risco , Transdução de Sinais/efeitos da radiação , Pele/efeitos dos fármacos , Pele/metabolismo , Fator de Transcrição AP-1/metabolismo
13.
Biofizika ; 59(6): 1093-6, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25715614

RESUMO

The evidence on the effect of different insulin-like growth factor concentrations on a state of human erythrocytes is provided. Activation of the insulin-like growth factor receptors led to changes in the conformation of hemoglobin, NO-transporting function in erythrocytes and also in micro-viscosity of the cell membrane. It was shown for the first time that at the binding of the insulin-like growth factor to a cell surface, hemoglobin of erythrocytes alters its conformations and affinity to ligands.


Assuntos
Membrana Eritrocítica/química , Heme/química , Hemoglobinas/química , Fator de Crescimento Insulin-Like I/química , Óxido Nítrico/química , Feminino , Humanos , Masculino
14.
Bull Exp Biol Med ; 155(2): 233-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24130998

RESUMO

Morphology of erythrocytes and conformation of hemoglobin-derived hematoporphyrin were studied in patients with coronary heart disease (CHD) and patients with circulatory failure using laser interference microscopy and Raman spectroscopy. Correlation was revealed (r=0.81) between hemoglobin oxygen saturation and oxyhemoglobin fraction in erythrocytes evaluated by Raman spectroscopy. Patients with CHD and patients with circulatory failure showed reduced oxygen-releasing capacity of hemoglobin and hemoglobin content and increased oxygen-binding capacity of hemoglobin, and hemoglobin affinity for oxygen. Significant differences from the control were observed only in patients with circulatory failure. It was found that hemoglobin content, hematocrit, and the shape of erythrocytes during CHD and circulatory failure did not differ from the control, whereas the area of erythrocytes was increased.


Assuntos
Doença das Coronárias/sangue , Eritrócitos Anormais/fisiologia , Hemoglobinas/química , Oxigênio/sangue , Choque/sangue , Adulto , Hematócrito , Hematoporfirinas , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio
15.
Biofizika ; 58(3): 501-6, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24159820

RESUMO

Different patterns of cell volume perturbations are commonly used for modes of cell death: necrosis (cell swelling) and apoptosis (cell shrinkage). In this study we employed recently developed three dimensional microscopy for the measurement of the volume of attached vascular smooth muscle cells transfected with E1A-adenoviral protein. These cells undergo rapid apoptosis in the absence of growth factors or in the presence of staurosporine. In 30-60 min of serum deprivation the volume of these cells is increased by -40% that corresponds to the time point of maximal activation of caspase 3 and chromatin cleavage. In 10-15 min swollen cells exhibit morphological collapse indicated by formation of apoptotic bodies. In contrast to serum-deprived cells, staurosporine leads to attenuation of cell volume by 30%. In this case, apoptotic bodies are detected in -2.5 hr after maximal shrinkage. Thus, our results show that cell shrinkage can not be considered as universal hallmark of apoptosis. The role of stimulus-specific cell volume perturbation in the triggering of the cell death machinery should be examined further.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Inibidores Enzimáticos/farmacologia , Imageamento Tridimensional/métodos , Estaurosporina/farmacologia , Animais , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Ratos
16.
Pflugers Arch ; 465(7): 977-83, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23377567

RESUMO

Previously, we reported that in mammalian erythrocytes irreversible annealing of spectrin heterodimers at 49-50 °C abolished cell volume-dependent regulation of ion carriers, thus suggesting an implication of a two-dimensional (2D) membrane carcass in volume sensing and/or signal transduction. To further examine this hypothesis, we employed atomic force microscopy. This method revealed folded membrane relief of fixed human erythrocytes with an average wave height of 3-5 nm covered by globular structures with a diameter of 40-50 nm and an average height of 1-2 nm. Erythrocyte swelling caused by reduction of medium osmolality decreased the height of membrane surface waves by 40 % and increased K(+),Cl(-) cotransport by approximately sixfold. Both volume-sensitive changes of membrane relief and activity of K(+),Cl(-) cotransporter were abolished by a 10-min preincubation at 50 °C. Our results strongly suggest that volume-dependent alterations of the human erythrocyte membrane relief are caused by reorganization of the 2D spectrin-actin network contributing to regulation of the activity of volume-sensitive ion transporters.


Assuntos
Membrana Celular/ultraestrutura , Eritrócitos/fisiologia , Temperatura Alta , Simportadores/metabolismo , Actinas/metabolismo , Membrana Celular/metabolismo , Cloretos/metabolismo , Eritrócitos/metabolismo , Humanos , Transporte de Íons , Microscopia de Força Atômica , Concentração Osmolar , Potássio/metabolismo , Espectrina/metabolismo , Cotransportadores de K e Cl-
18.
Bull Exp Biol Med ; 153(4): 508-12, 2012 Aug.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-22977857

RESUMO

Oxygen-binding properties of erythrocyte hemoglobin were studied in children with type 1 diabetes mellitus by Raman spectroscopy. The content of hemoglobin-oxygen complexes increased significantly only in children with lasting disease (more than 1 year); oxygen-binding capacity of hemoglobin is significantly changed, while its capacity to release oxygen remained unchanged. These changes were paralleled by alteration of hemoglobin affinity for oxygen. The area and content of hemoglobin were studied by laser interference microscopy. Hemoglobin content increased significantly in erythrocytes of patients with a more than 1-year history of type 1 diabetes mellitus. In these children, a significant inverse correlation between oxyhemoglobin fraction, oxygen binding capacity, and cholesterol content was found, this clinical parameter positively correlated with affinity for oxygen measured by Raman spectroscopy.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Eritrócitos/metabolismo , Hemoglobinas/metabolismo , Oxigênio/metabolismo , Oxiemoglobinas/metabolismo , Adolescente , Criança , Pré-Escolar , Colesterol/sangue , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Masculino , Microscopia Confocal , Análise Espectral Raman , Estatísticas não Paramétricas , Fatores de Tempo
19.
Mol Biol (Mosk) ; 46(1): 147-55, 2012.
Artigo em Russo | MEDLINE | ID: mdl-22642112

RESUMO

Prokaryotic cells, including cyanobacteria, respond to a decrease in ambient temperature by activation of numerous cold shock genes. Low temperatures cause a decrease in membrane fluidity, which is maintained at some optimal level mainly by fatty acid (FA) desaturases. Here, temperature-dependent expression of the desB gene for the omega3-desaturase in Synechocystis, which synthesized polyunsaturated FAs, and in its mutant, desA-/desD-, which is defective in genes for delta12- and delta6-desaturases and is capable of synthesizing only monounsaturated FAs was studied. Low temperatures caused the increase in the amount of the desB mRNA in the wild-type cells with the maximum observed at 24 degrees C. In the double mutant desA-/desD- cells, the maximum amount of this mRNA was accumulated at 28-30 degrees C. Thus, our studies of the desB gene for the omega3-desaturase demonstrated that temperature-dependent expression of genes, which are responsible for the maintenance of the optimal membrane fluidity, depends on physical state of these membranes and is regulated by a feedback mode.


Assuntos
Cianobactérias/genética , Cianobactérias/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Cianobactérias/fisiologia , Ácidos Graxos Dessaturases/isolamento & purificação , Ácidos Graxos Ômega-3/biossíntese , Ácidos Graxos Ômega-3/genética , Retroalimentação Fisiológica , Regulação da Expressão Gênica/fisiologia , Fluidez de Membrana/genética , Fluidez de Membrana/fisiologia , Mutação , Temperatura
20.
Kardiologiia ; 51(11): 28-37, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22117768

RESUMO

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Glutationa , Hipertensão/tratamento farmacológico , Ferro , Óxidos de Nitrogênio , S-Nitrosoglutationa/farmacocinética , Nitrito de Sódio/farmacocinética , Adulto , Animais , Disponibilidade Biológica , Avaliação Pré-Clínica de Medicamentos/métodos , Monitoramento de Medicamentos/métodos , Glutationa/administração & dosagem , Glutationa/efeitos adversos , Glutationa/farmacocinética , Glutationa/farmacologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipotensão/induzido quimicamente , Infusões Intravenosas , Ferro/administração & dosagem , Ferro/efeitos adversos , Ferro/farmacocinética , Ferro/farmacologia , Masculino , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/administração & dosagem , Óxidos de Nitrogênio/efeitos adversos , Óxidos de Nitrogênio/farmacocinética , Óxidos de Nitrogênio/farmacologia , Ratos , Ratos Wistar , Equivalência Terapêutica , Terapias em Estudo , Resultado do Tratamento
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