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1.
Lasers Med Sci ; 39(1): 122, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703271

RESUMO

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.


Assuntos
Lasers de Corante , Animais , Ratos , Masculino , Lasers de Corante/uso terapêutico , Miócitos de Músculo Liso/fisiologia , Miócitos de Músculo Liso/efeitos da radiação , Vasodilatação/efeitos da radiação , Vasodilatação/fisiologia , Temperatura , Músculo Liso Vascular/efeitos da radiação , Músculo Liso Vascular/fisiologia , Células Endoteliais/efeitos da radiação , Células Endoteliais/fisiologia , Vasoconstrição/efeitos da radiação , Vasoconstrição/fisiologia , Endotélio Vascular/efeitos da radiação , Ratos Wistar
2.
PLoS One ; 16(10): e0257896, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34610026

RESUMO

INTRODUCTION: Peripheral artery disease (PAD) is a highly morbid condition in which impaired blood flow to the limbs leads to pain and tissue loss. Previously we identified 670 nm electromagnetic energy (R/NIR) to increase nitric oxide levels in cells and tissue. NO elicits relaxation of smooth muscle (SMC) by stimulating potassium efflux and membrane hyperpolarization. The actions of energy on ion channel activity have yet to be explored. Here we hypothesized R/NIR stimulates vasodilation through activation of potassium channels in SMC. METHODS: Femoral arteries or facial arteries from C57Bl/6 and Slo1-/- mice were isolated, pressurized to 60 mmHg, pre-constricted with U46619, and irradiated twice with energy R/NIR (10 mW/cm2 for 5 min) with a 10 min dark period between irradiations. Single-channel K+ currents were recorded at room temperature from cell-attached and excised inside-out membrane patches of freshly isolated mouse femoral arterial muscle cells using the patch-clamp technique. RESULTS: R/NIR stimulated vasodilation requires functional activation of the large conductance potassium channels. There is a voltage dependent outward current in SMC with light stimulation, which is due to increases in the open state probability of channel opening. R/NIR modulation of channel opening is eliminated pharmacologically (paxilline) and genetically (BKca α subunit knockout). There is no direct action of light to modulate channel activity as excised patches did not increase the open state probability of channel opening. CONCLUSION: R/NIR vasodilation requires indirect activation of the BKca channel.


Assuntos
Radiação Eletromagnética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos da radiação , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Vasodilatação/efeitos da radiação , Animais , Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/métodos , Artéria Femoral/metabolismo , Técnicas de Inativação de Genes , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Potenciais da Membrana/efeitos da radiação , Camundongos , Camundongos Knockout , Óxido Nítrico/metabolismo , Técnicas de Patch-Clamp , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/terapia
3.
Biochem Pharmacol ; 159: 121-139, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508525

RESUMO

Ionizing radiation (IR) leads to a variety of the cardiovascular diseases, including the arterial hypertension. A number of studies have demonstrated that blood vessels represent important target for IR, and the endothelium is one of the most vulnerable components of the vascular wall. IR causes an inhibition of nitric oxide (NO)-mediated endothelium-dependent vasodilatation and generation of reactive oxygen (ROS) and nitrogen (RNS) species trigger this process. Inhibition of NO-mediated vasodilatation could be due to endothelial NO synthase (eNOS) down-regulation, inactivation of endothelium-derived NO, and abnormalities in diffusion of NO from the endothelial cells (ECs) leading to a decrease in NO bioavailability. Beside this, IR suppresses endothelial large conductance Ca2+-activated K+ channels (BKCa) activity, which control NO synthesis. IR also leads to inhibition of the BKCa current in vascular smooth muscle cells (SMCs) which is mediated by protein kinase C (PKC). On the other hand, IR-evoked enhanced vascular contractility may result from PKC-mediated increase in SMCs myofilament Ca2+ sensitivity. Also, IR evokes vascular wall inflammation and atherosclerosis development. Vascular function damaged by IR can be effectively restored by quercetin-filled phosphatidylcholine liposomes and mesenchymal stem cells injection. Using RNA-interference technique targeted to different PKC isoforms can also be a perspective approach for pharmacological treatment of IR-induced vascular dysfunction.


Assuntos
Aterosclerose/etiologia , Radiação Ionizante , Vasodilatação/efeitos da radiação , Animais , Aterosclerose/fisiopatologia , Células Endoteliais/metabolismo , Células Endoteliais/efeitos da radiação , Endotélio Vascular/fisiopatologia , Humanos , Canais Iônicos/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos da radiação , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
4.
JCI Insight ; 3(15)2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30089722

RESUMO

The long-term adverse effects of radiotherapy on cardiovascular disease are well documented. However, the underlying mechanisms responsible for this increased risk are poorly understood. Previous studies using rigorous smooth muscle cell (SMC) lineage tracing have shown abundant SMC investment into atherosclerotic lesions, where SMCs contribute to the formation of a protective fibrous cap. Studies herein tested whether radiation impairs protective adaptive SMC responses during vascular disease. To do this, we exposed SMC lineage tracing (Myh11-ERT2Cre YFP+) mice to lethal radiation (1,200 cGy) followed by bone marrow transplantation prior to atherosclerosis development or vessel injury. Surprisingly, following irradiation, we observed a complete loss of SMC investment in 100% of brachiocephalic artery (BCA), carotid artery, and aortic arch lesions. Importantly, this was associated with a decrease in multiple indices of atherosclerotic lesion stability within the BCA. Interestingly, we observed anatomic heterogeneity, as SMCs accumulated normally into lesions of the aortic root and abdominal aorta, suggesting that SMC sensitivity to lethal irradiation occurs in blood vessels of neural crest origin. Taken together, these results reveal an undefined and unintended variable in previous studies using lethal irradiation and may help explain why patients exposed to radiation have increased risk for cardiovascular disease.


Assuntos
Aterosclerose/patologia , Tronco Braquiocefálico/efeitos da radiação , Músculo Liso Vascular/efeitos da radiação , Miócitos de Músculo Liso/efeitos da radiação , Animais , Aorta Abdominal/patologia , Aorta Abdominal/efeitos da radiação , Aterosclerose/etiologia , Medula Óssea/efeitos da radiação , Transplante de Medula Óssea , Tronco Braquiocefálico/patologia , Diferenciação Celular/efeitos da radiação , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Knockout para ApoE , Músculo Liso Vascular/citologia , Irradiação Corporal Total
5.
Chembiochem ; 19(12): 1312-1318, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29417721

RESUMO

Diazeniumdiolates (NONOates) are a class of nitric-oxide-releasing substances widely used in studies of NO/cGMP signalling. Because spatiotemporal control is highly desirable for such purposes, we have synthesised a new Npom-caged pyrrolidine NONOate. A kinetic analysis together with a Griess assay showed the photodependent release of NO with high quantum yield (UV light). In primary vascular smooth muscle cells (VSMCs), our compound was reliably able to induce fast increases in cGMP, as measured with a genetically encoded FRET-based cGMP sensor and further validated by the phosphorylation of the downstream target vasodilator-stimulated phosphoprotein (VASP). Thanks to their facile synthesis, good decaging kinetics and capability to activate cGMP signalling in a fast and efficient manner, Npom-protected NONOates allow for improved spatiotemporal control of NO/cGMP signalling.


Assuntos
Compostos Azo/farmacologia , GMP Cíclico/metabolismo , Músculo Liso Vascular/citologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Animais , Compostos Azo/química , Células Cultivadas , Camundongos Transgênicos , Modelos Moleculares , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos da radiação , Doadores de Óxido Nítrico/química , Pirrolidinas/química , Pirrolidinas/farmacologia , Raios Ultravioleta
6.
J Vasc Access ; 19(2): 153-161, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29192723

RESUMO

PURPOSE: To study the effect of x-ray radiotherapy on vascular smooth muscle cells (VSMCs) and elucidate the mechanisms in preventing neointimal hyperplasia of prosthetic vascular grafts. MATERIALS AND METHODS: In model I, twelve mongrel dogs underwent revascularization with prosthetic grafts and half the dogs underwent irradiation of the grafts at 28 Gy. In model II, human VSMCs (hVSMCs) were maintained and divided into six groups to which external radiation was applied at six different doses: 0 Gy, 2 Gy, 8 Gy, 16 Gy, 24 Gy and 30 Gy. In both models, specimens were harvested and examined by using morphological, immunological, cellular and molecular methods. RESULTS: After irradiation, the neointima thickness was significantly lower in irradiated groups (p≤0.01). The radiotherapy could up-regulate p27kip1, and down-regulate proliferating cell nuclear antigen (PCNA) and S phase kinase associated protein 2 (Skp2). X-ray irradiation inhibits the proliferation of hVSMCs via acting on G1/S phase of cell cycle. The apoptosis of hVSMCs increased significantly with dose and time. The expression of PCNA and Skp2 were decreased after a first increasing trend with dose, but had a significant negative correlation with time. The expression of p27kip1 had a significant positive correlation with dose and time. CONCLUSIONS: Postoperative external fractionated irradiation after prosthetic vessel replacement of the abdominal aorta suppressed the development of hyperplasia in the graft neointima in the short term. There was a prominent time- and dose-dependent inhibition of VSMC proliferation by radiation when it was administered.


Assuntos
Aorta Abdominal/efeitos da radiação , Aorta Abdominal/cirurgia , Apoptose/efeitos dos fármacos , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Proliferação de Células/efeitos da radiação , Músculo Liso Vascular/efeitos da radiação , Músculo Liso Vascular/cirurgia , Miócitos de Músculo Liso/efeitos da radiação , Neointima , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Implante de Prótese Vascular/efeitos adversos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Cães , Relação Dose-Resposta à Radiação , Humanos , Hiperplasia , Modelos Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Fatores de Tempo
7.
Am J Physiol Lung Cell Mol Physiol ; 314(1): L93-L106, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28882814

RESUMO

We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the nonvisual G protein-coupled receptor melanopsin (Opsin 4; Opn4). Here we tested the hypothesis that nonvisual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G protein-coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2, as demonstrated with a proximity ligation assay. Light elicited an intensity-dependent relaxation of PAs preconstricted with phenylephrine (PE), with a maximum response between 400 and 460 nm (blue light). Wavelength-specific photorelaxation was attenuated in PAs from Opn4-/- mice and further reduced following shRNA-mediated knockdown of Opn3. Inhibition of GRK2 amplified the response and prevented physiological desensitization to repeated light exposure. Blue light also prevented PE-induced constriction in isolated PAs, decreased basal tone, ablated PE-induced single-cell contraction of PASMCs, and reversed PE-induced depolarization in PASMCs when GRK2 was inhibited. The photorelaxation response was modulated by soluble guanylyl cyclase but not by protein kinase G or nitric oxide. Most importantly, blue light induced significant vasorelaxation of PAs from rats with chronic pulmonary hypertension and effectively lowered pulmonary arterial pressure in isolated intact perfused rat lungs subjected to acute hypoxia. These findings show that functional Opn3 and Opn4 in PAs represent an endogenous "optogenetic system" that mediates photorelaxation in the pulmonary vasculature. Phototherapy in conjunction with GRK2 inhibition could therefore provide an alternative treatment strategy for pulmonary vasoconstrictive disorders.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Hipertensão Pulmonar/radioterapia , Fototerapia , Artéria Pulmonar/efeitos da radiação , Opsinas de Bastonetes/fisiologia , Vasodilatação/efeitos da radiação , Animais , Células Cultivadas , Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipóxia/complicações , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos da radiação , Óxido Nítrico/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Guanilil Ciclase Solúvel/genética , Guanilil Ciclase Solúvel/metabolismo , Vasodilatação/fisiologia
8.
Environ Toxicol Pharmacol ; 54: 177-183, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28755625

RESUMO

INTRODUCTION: It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. METHODS: We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. RESULTS: The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. DISCUSSION: Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury.


Assuntos
Contração Muscular/efeitos da radiação , Músculo Liso Vascular/efeitos da radiação , Traumatismos dos Nervos Periféricos/radioterapia , Animais , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Regulação da Expressão Gênica/efeitos da radiação , Masculino , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos da radiação , Transcriptoma/efeitos da radiação , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Raios X
9.
Sci Rep ; 6: 21683, 2016 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-26899550

RESUMO

Paclitaxel (PTX) has been recognized as a promising drug for intervention of vascular reconstructions. However, it is still difficult to achieve local drug delivery in a spatio-temporally controllable manner under real-time image guidance. Here, we introduce an ultrasound (US) triggered image-guided drug delivery approach to inhibit vascular reconstruction via paclitaxel (PTX)-loaded microbubbles (PLM) in a rabbit iliac balloon injury model. PLM was prepared through encapsulating PTX in the shell of lipid microbubbles via film hydration and mechanical vibration technique. Our results showed PLM could effectively deliver PTX when exposed to US irradiation and result in significantly lower viability of vascular smooth muscle cells. Ultrasonographic examinations revealed the US signals from PLM in the iliac artery were greatly increased after intravenous administration of PLM, making it possible to identify the restenosis regions of iliac artery. The in vivo anti-restenosis experiments with PLM and US greatly inhibited neointimal hyperplasia at the injured site, showing an increased lumen area and reduced the ratio of intima area and the media area (I/M ratio). No obvious functional damages to liver and kidney were observed for those animals. Our study provided a promising approach to realize US triggered image-guided PTX delivery for therapeutic applications against iliac restenosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Constrição Patológica/terapia , Sistemas de Liberação de Medicamentos/métodos , Artéria Ilíaca/efeitos dos fármacos , Microbolhas , Paclitaxel/farmacologia , Animais , Constrição Patológica/patologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Artéria Ilíaca/patologia , Músculo Liso Vascular/efeitos da radiação , Miócitos de Músculo Liso/efeitos da radiação , Coelhos , Ondas Ultrassônicas
10.
Toxicol Sci ; 144(1): 138-50, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25516496

RESUMO

Because of high exposure to systemic noxae, vascular endothelial cells (EC) have to ensure distinct damage defense and regenerative mechanisms to guarantee vascular health. For meaningful toxicological drug assessments employing embryonic stem cell (ESC)-based in vitro models, functional competence of differentiated progeny and detailed knowledge regarding damage defense mechanisms are essential. Here, mouse ESCs (mESC) were differentiated into functionally competent vascular cells (EC and smooth muscle cells [SMC]). mESC, EC, and SMC were comparatively analyzed regarding DNA repair and DNA damage response (DDR). Differentiation was accompanied by both congruent and unique alterations in repair and DDR characteristics. EC and SMC shared the downregulation of genes involved cell cycle regulation and repair of DNA double-strand breaks (DSBs) and mismatches, whereas genes associated with nucleotide excision repair (NER), apoptosis, and autophagy were upregulated when compared with mESC. Expression of genes involved in base excision repair (BER) was particularly low in SMC. IR-induced formation of DSBs, as detected by nuclear γH2AX foci formation, was most efficient in SMC, the repair of DSBs was fastest in EC. Together with substantial differences in IR-induced phosphorylation of p53, Chk1, and Kap1, the data demonstrate complex alterations in DDR capacity going along with the loss of pluripotency and gain of EC- and SMC-specific functions. Notably, IR exposure of early vascular progenitors did not impair differentiation into functionally competent EC and SMC. Summarizing, mESC-based vascular differentiation models are informative to study the impact of environmental stressors on differentiation and function of vascular cells.


Assuntos
Diferenciação Celular/efeitos da radiação , Células-Tronco Embrionárias/efeitos da radiação , Células Progenitoras Endoteliais/efeitos da radiação , Músculo Liso Vascular/efeitos da radiação , Miócitos de Músculo Liso/efeitos da radiação , Células-Tronco Pluripotentes/efeitos da radiação , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/genética , Autofagia/efeitos da radiação , Biomarcadores/metabolismo , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/patologia , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Regulação da Expressão Gênica , Histonas/metabolismo , Camundongos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neovascularização Fisiológica/genética , Neovascularização Fisiológica/efeitos da radiação , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/patologia , RNA Mensageiro/metabolismo , Fatores de Tempo
11.
Bull Exp Biol Med ; 157(4): 440-2, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25110078

RESUMO

We studied disorders in ciliary body microcirculation in experimental chronic glomerulonephritis with tubulointerstitial nephritis and evaluated the hemodynamic effects of low-frequency pulsed electromagnetic field in this pathology. Laser Doppler flowmetry demonstrated vasospasm with reduced nutrient blood fl ow in the ciliary body of animals with experimental chronic glomerulonephritis with tubulointerstitial nephritis. The exposure to low-frequency pulsed electromagnetic field using developed technology will lead to significant reduction of the vascular tone and improve arterial blood supply to the microcirculatory bed.


Assuntos
Corpo Ciliar/efeitos da radiação , Glomerulonefrite/fisiopatologia , Microcirculação/efeitos da radiação , Músculo Liso Vascular/efeitos da radiação , Nefrite Intersticial/fisiopatologia , Espasmo/radioterapia , Animais , Chinchila , Corpo Ciliar/irrigação sanguínea , Corpo Ciliar/fisiopatologia , Radiação Eletromagnética , Fluxometria por Laser-Doppler , Masculino , Músculo Liso Vascular/fisiopatologia , Espasmo/fisiopatologia
12.
J Photochem Photobiol B ; 114: 73-8, 2012 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-22695226

RESUMO

Dental resin curing blue light has been used in the treatment of tooth bleaching and to restore teeth with resin-based composite fillings. However, there has been little consideration of its effect on oral tissues such as dental pulp and oral mucosa. The aim of this study was to investigate whether dental resin curing blue light irradiation affects the dental pulp, especially the blood vessels that are known as the first target of reactive oxygen species (ROS), which play an important role in vascular reactivity. We found that blue light irradiation increased the level of lipid peroxidation in isolated rat aorta blood vessels by measuring malondialdehyde. Furthermore, cell proliferative activity was decreased in a time-dependent manner and apoptosis of human aorta vascular smooth muscle cells (VSMCs) was induced. These results indicated that (ROS) such as hydrogen peroxide and hydroxyl radicals were generated in VSMCs by irradiation with blue light, and they induced cytotoxicity associated with oxidative stress, which increased lipid peroxidation and apoptosis. In addition, N-acetyl-l-cysteine, which is a typical intracellular antioxidant, protected VSMCs against cytotoxicity associated with oxidative stress. These findings suggested that antioxidants may be used to prevent oxidative stress in dental pulp by repeated and/or multiple treatments with blue light irradiation in future dental treatments.


Assuntos
Luz , Músculo Liso Vascular/metabolismo , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Resinas Sintéticas/química , Acetilcisteína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Resinas Sintéticas/farmacologia
13.
Vascul Pharmacol ; 56(3-4): 142-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22226998

RESUMO

It is likely that large-conductance Ca²âº-activated K⁺ (BK(Ca)) channels channelopathy tightly involved in vascular malfunctions and arterial hypertension development. In the present study, we compared the results of siRNAs-induced α-BK(Ca) gene silencing and vascular abnormalities produced by whole-body ionized irradiation in rats. The experimental design comprised RT-PCR and patch clamp technique, thoracic aorta smooth muscle (SM) contractile recordings and arterial blood pressure (BP) measurements on the 30th day after whole body irradiation (6Gy) and following siRNAs KCNMA1 gene silencing in vivo. The expression profile of BK(Ca) mRNA transcripts in SM was significantly decreased in siRNAs-treated rats in a manner similar to irradiated SM. In contrast, the mRNA levels of K(v) and K(ATP) were significantly increased while L-type calcium channels mRNA transcripts demonstrated tendency to increment. The SMCs obtained from irradiated animals and after KCNMA1 gene silencing showed a significant decrease in total K⁺ current density amplitude. Paxilline (500 nM)-sensitive components of outward current were significantly decreased in both irradiated and gene silencing SMCs. KCNMA1 gene silencing increased SM sensitivity to norepinephrine while Ach-induced relaxation had decreased. The silencing of KCNMA1 had no significant effect on BP while radiation produced sustained arterial hypertension. Therefore, radiation alters the form and function of the BK(Ca) channel and this type of channelopathy may contribute to related vascular abnormalities. Nevertheless, it is unlikely that BK(Ca) can operate as a crucial factor for radiation-induced arterial hypertension.


Assuntos
Aorta Torácica/metabolismo , Hipertensão/etiologia , Hipertensão/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/antagonistas & inibidores , Músculo Liso Vascular/metabolismo , Lesões por Radiação/fisiopatologia , Vasoconstrição , Animais , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Aorta Torácica/efeitos da radiação , Pressão Sanguínea/efeitos da radiação , Células Cultivadas , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos da radiação , Inativação Gênica , Hipertensão/fisiopatologia , Técnicas In Vitro , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Masculino , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Músculo Liso Vascular/efeitos da radiação , Norepinefrina/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/química , Canais de Potássio/genética , Canais de Potássio/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacos
14.
Fiziol Zh (1994) ; 58(6): 36-47, 2012.
Artigo em Ucraniano | MEDLINE | ID: mdl-23530412

RESUMO

The study was conducted on three groups of rats: Group I included Wistar rats with normal blood pressure (first control group); group II - rats with genetically determined hypertension (second control group); group Ill - rats with genetically determined hypertension under the influence ofmagnetic-laser power (study group). For the low-intensively magnetic-laser influence (MLI) we have used device MIT-MT, Ukraine, which was designed for the treatment of low-frequency magnetic field using optical flow blue and red ranges of spectrum. The MLI duration was 15 minutes for the blue range, and 25 minutes for the red one. Biochemical studies included the determination of the activity of isoenzymes of NO-synthase: constitutive (cNOS) and inducible (iNOS), the content of free hemoglobin, stable metabolites of NO, namely nitrite - (NO2(-)) and nitrate - (NO3(-)) anions, resistance to acid hemolysis of red blood cells. The contractile activity of smooth muscles of the aorta was measured. We found that magnetic-laser exposure of rats with genetically determined hypertension in the red (630 nm) and blue (470 nm wavelength) optical range even after a single session leads to an increased synthesis of nitric oxide in the blood plasma. Our data sindicate that the most effective in the intensification of endogenous nitric oxide (increase of NO2(-) and reduction of NO3(-)) and endothelium-dependent responses of aorta in rats with genetically determined hypertension was a ten-day course of the magnetic-laser exposure in the optical flow of the blue spectral range. Also, after 10 sessions of magnetic-laser exposure in rats from the above specified spectrum a stabilization of erythrocyte membranes was observed.


Assuntos
Aorta/efeitos da radiação , Hipertensão/radioterapia , Terapia com Luz de Baixa Intensidade , Magnetoterapia , Contração Muscular/efeitos da radiação , Músculo Liso Vascular/efeitos da radiação , Óxido Nítrico/sangue , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiopatologia , Eritrócitos/efeitos da radiação , Hemoglobinas/metabolismo , Hemólise/efeitos da radiação , Hipertensão/sangue , Hipertensão/fisiopatologia , Lasers , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Nitritos/metabolismo , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
15.
Fiziol Zh (1994) ; 57(4): 46-56, 2011.
Artigo em Ucraniano | MEDLINE | ID: mdl-22164408

RESUMO

The goal of this study was to determine the cellular mechanisms of vascular endothelial dysfunction in rats irradiated with gamma-rays. Acetylcholine (Ach)-induced relaxation of rat thoracic aorta rings was measured as a test of endothelial integrity and function. The data obtained allow suggest that endothelial function is impaired in aorta from g-irradiated rats mainly due to the loss of EDRF/NO-dependent, but not EDHF-dependent relaxation. It has been shown that r-irradiation reduced the Ach-induced NO-release measured as nitrite anion content. Experiments on isolated rat aortic smooth muscle cells using whole-cell patch clamp technique demonstrated that irradiation led to a significant decrease in outward potassium currents. However, gamma-ray irradiation was without effect on K(+)-current carried through apamine-sensitive channels while the current through charybdotoxin-sensitive channels was increased as compared to cells from control animals. The data suggest that EDHF is resistant to ionized radiation and may constitute a crucial reserve mechanism for maintenance of blood flow under radiation. Therefore, it is likely that the subsequent studies related to EDHF identification will be important for new drugs development and targeted pharmacological intervention at endothelium dysfunction in case of radiation impact.


Assuntos
Aorta Torácica/efeitos da radiação , Fatores Biológicos/metabolismo , Endotélio Vascular/efeitos da radiação , Raios gama , Músculo Liso Vascular/efeitos da radiação , Vasodilatação/efeitos da radiação , Animais , Aorta Torácica/metabolismo , Endotélio Vascular/metabolismo , Masculino , Potenciais da Membrana/efeitos da radiação , Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Canais de Potássio/metabolismo , Ratos , Ratos Wistar
16.
Int J Radiat Oncol Biol Phys ; 81(1): 262-9, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21605947

RESUMO

PURPOSE: To investigate whether occurrence of early radiation effects in lung tissue depends on local dose only. METHODS AND MATERIALS: Twenty-five percent, 50%, 66%, 88%, or 100% of the rat lung was irradiated using single fractions of 150-MeV protons. For all volumes, in-field and out-of-field dose-response curves were obtained 8 weeks after irradiation. The pathohistology of parenchymal inflammation, infiltrates, fibrosis, and vascular damage and the relative expression of proinflammatory cytokines interleukin (IL)-1α, transforming growth factor-ß, IL-6, and tumor necrosis factor-α were assessed. RESULTS: For all histologic endpoints, irradiated dose- and volume-dependent in-field and out-of-field effects were observed, albeit with different dynamics. Of note, the out-of-field effects for vascular damage were very similar to the in-field effects. Interestingly, only IL-6 showed a clear dose-dependent increase in expression both in-field and out-of-field, whereas the expression levels of IL-1α, transforming growth factor-ß, and tumor necrosis factor-α were either very low or without a clear dose-volume relation. As such, none of the radiation effects studied depended only on local dose to the tissue. CONCLUSION: The effects of radiation to lung tissue do not only depend on local dose to that tissue. Especially at high-volume irradiation, lung damage seems to present globally rather than locally. The accuracy of predictive modeling may be improved by including nonlocal effects.


Assuntos
Pulmão/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Animais , Relação Dose-Resposta à Radiação , Interleucina-1alfa/metabolismo , Interleucina-6/metabolismo , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Masculino , Modelos Biológicos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos da radiação , Miócitos de Músculo Liso/efeitos da radiação , Prótons , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Lesões Experimentais por Radiação/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
J Vasc Interv Radiol ; 22(5): 623-9, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21414804

RESUMO

PURPOSE: Restenosis is still one of the major limitations after angioplasty. A therapeutic treatment combining ß-irradiation and pharmacologic cyclooxygenase-2 inhibition was employed to study the impact on vascular smooth muscle cells (SMCs). MATERIALS AND METHODS: The effects of meclofenamic acid in combination with yttrium-90 ((90)Y) on cell growth, clonogenic activity, cell migration, and cell cycle distribution of human aortic SMCs were investigated. Treatment was sustained over a period of 4 days and recovery of cells was determined until day 20 after initiation. The hypothesis was that there is no difference between control and treated groups. RESULTS: A dose-dependent growth inhibition was observed in single and combined treatment groups for meclofenamic acid and ß-irradiation. Cumulative radiation dosage of 8 Gy completely inhibited colony formation. This was also observed for 200 µM meclofenamic acid alone or in combination with minor ß-irradiation dosages. Results of the migration tests showed also a dose dependency with additive effects of combined therapy. Meclofenamic acid 200 µM alone and with cumulative ß-irradiation dosages resulted in an increased G2/M-phase share. CONCLUSIONS: Incubating human SMCs with meclofenamic acid and (90)Y for a period of 4 d (ie, 1.5 half-life times) resulted in an effective inhibition of smooth muscle cell proliferation, colony formation, and migration.


Assuntos
Arteriopatias Oclusivas/prevenção & controle , Braquiterapia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ácido Meclofenâmico/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos da radiação , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos da radiação , Radioisótopos de Ítrio , Angioplastia com Balão/efeitos adversos , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/patologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Células Cultivadas , Terapia Combinada , Constrição Patológica , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Humanos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Prevenção Secundária , Fatores de Tempo
19.
Fiziol Zh (1994) ; 56(4): 47-58, 2010.
Artigo em Ucraniano | MEDLINE | ID: mdl-20968037

RESUMO

Peculiarities of changes in the vascular reactivity and in the content of reactive forms of oxygen and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of C57BL/6 and BALB/c mice of the two age groups (6 and 18 mo.), which were born and permanently kept in the Chernobyl alienation zone. The results obtained showed a disturbance of acetylcholine-induced endothelium-dependent reactions of relaxation of smooth muscles of the thoracic aorta. A lower level of NO synthesis and lower level of oxidative arginase metabolism of arginine corresponded to a higher degree of damage of endothelium-dependent reactions of relaxation of the thoracic aorta smooth muscles. A decrease of NO synthesis in conditions of permanent effects of low doses of radiation was conditioned by an increase of generation of reactive forms of oxygen, namely, superoxide and hydroxyl radicals, which might be formed in mitochondria. In conditions of permanent effects of low doses of radiation a lesser level of protein nitrosothilation, same as lesser one of generation of OH-radical, corresponded to a higher level of damage of endothelium-dependent reactions.


Assuntos
Aorta Torácica/efeitos da radiação , Acidente Nuclear de Chernobyl , Espécies Reativas de Oxigênio/metabolismo , Vasodilatação/efeitos da radiação , Adaptação Fisiológica/efeitos da radiação , Animais , Aorta Torácica/metabolismo , Relação Dose-Resposta à Radiação , Endotélio Vascular/metabolismo , Endotélio Vascular/efeitos da radiação , Feminino , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos da radiação , Óxido Nítrico/biossíntese , Especificidade da Espécie , Fatores de Tempo , Ucrânia
20.
Int J Radiat Oncol Biol Phys ; 77(5): 1545-52, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-20646873

RESUMO

PURPOSE: The purpose is to evaluate effects of a new radiotherapy protocol, microbeam radiation therapy, on the artery wall. In previous studies on animal models, it was shown that capillaries recover well from hectogray doses of X-rays delivered in arrays of narrow (< or = 50 microm) beams with a minimum spacing of 200 microm. Here, short- and long-term effects of comparable microplanar beam configurations on the saphenous artery of the mouse hind leg were analyzed in situ by use of nonlinear optics and compared with histopathologic findings. METHODS AND MATERIALS: The left hind leg of normal mice including the saphenous artery was irradiated by an array of 26 microbeams of synchrotron X-rays (50 microm wide, spaced 400 microm on center) with peak entrance doses of 312 Gy and 2,000 Gy. RESULTS: The artery remained patent, but narrow arterial smooth muscle cell layer segments that were in the microplanar beam paths became atrophic and fibrotic in a dose-dependent pattern. The wide tunica media segments between those paths hypertrophied, as observed in situ by two-photon microscopy and histopathologically. CONCLUSIONS: Clinical risks of long-delayed disruption or occlusion of nontargeted arteries from microbeam radiation therapy will prove less than corresponding risks from broad-beam radiosurgery, especially if peak doses are kept below 3 hectograys.


Assuntos
Membro Posterior/irrigação sanguínea , Músculo Liso Vascular/efeitos da radiação , Tolerância a Radiação/fisiologia , Túnica Média/efeitos da radiação , Animais , Artérias/patologia , Artérias/efeitos da radiação , Fibrose , Camundongos , Camundongos Endogâmicos BALB C , Microscopia/métodos , Músculo Liso Vascular/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Doses de Radiação , Lesões Experimentais por Radiação/patologia , Radioterapia/métodos , Túnica Média/patologia
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