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1.
Article in Chinese | WPRIM | ID: wpr-888151

ABSTRACT

This study aimed to observe the inhibitory effect of icariin against oxidative stress-induced calcification in aortic vascular smooth muscle cells(VSMCs) and elucidate the molecular mechanism of icariin in inhibiting endoplasmic reticulum stress(ERS)-mediated atherosclerotic calcification, so as to provide new ideas for exploring the anti-atherosclerotic mechanism of Epimedii Folium. The VSMCs in rat thoracic aorta were subjected to adherent culture and then treated with the complete calcification DMEM containing high glucose and hydrogen peroxide(H_2O_2) for three weeks. The resulting calcified VSMCs were divided into different treatment groups. Icariin was added one week after calcification induction for protecting the VSMCs, whose viability was then detected using cell counting kit-8(CCK-8). Alizarin red-S staining was conducted to observe the calcification degree. The activity of alkaline phosphatase(ALP) in VSMCs was measured using the disodium phenyl phosphate substrate and the calcium content was measured by arsenazo Ⅲ method. The mRNA expression levels of ossification-related factors including osteocalcin(OC), osteopontin(OPN), Runt-related transcription factor 2(Runx2), and type Ⅰ collagen(Col Ⅰa) were detected by real-time PCR. Western blot was carried out to determine the protein expression levels of α-smooth muscle actin(α-SMA), Runx2, activating transcription factor 4(ATF4), and eukaryotic translation initiation factor(eIF)-2α. The results showed that H_2O_2 significantly induced the calcification of VSMCs, increased the ALP activity and calcium content in VSMCs, promoted OC, OPN, Runx2, and Col Ⅰa mRNA expression and Runx2 protein expression, and reduced α-SMA protein expression. The ATF4 protein expression and eIF2α phosphorylation were also elevated significantly. Icariin reversed the calcification of VSMCs induced by H_2O_2, inhibited ALP activity and calcium content in VSMCs, down-regulated the mRNA expression levels of OC, OPN, Runx2 and Col Ⅰa and Runx2 protein expression, and relatively up-regulated the expression of α-SMA. The expression of ATF4 and phosphorylation of eIF2α also declined significantly. All these have demonstrated that icariin inhibited VSMCs calcification by down-regulating the ossification-related factors and lowering ALP activity and calcium content in VSMCs. Besides, the down-regulation of Runx2 expression and the inhibition of ATF4 and eIF2α-mediated cellular calcification pathway in ERS might also be involved in such calcification-suppressing process.


Subject(s)
Animals , Cells, Cultured , Flavonoids/pharmacology , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle , Oxidative Stress , Rats
2.
Article in Chinese | WPRIM | ID: wpr-921566

ABSTRACT

Abdominal aortic aneurysm(AAA)is a common aortic degenerative disease in the elderly,and its incidence is gradually increasing with the aging of the population.There are no specific drugs available to delay the expansion of AAA.Once the aneurysm ruptures,the mortality will exceed 90%,which seriously threatens the life of patients.Given the high incidence of AAA in the elderly,this review discusses the role of vascular aging in the pathogenesis of AAA,involving chronic inflammation,oxidative stress,mitochondrial dysfunction,protein homeostasis imbalance,increased apoptosis and necrosis,extracellular matrix remodeling,nutritional sensing disorders,epigenetic changes,and increased pro-aging factors.Meanwhile,several potential aging-related drug targets of AAA are listed.This review provides new ideas for basic and translational medical research of AAA.


Subject(s)
Aged , Aging , Animals , Aorta, Abdominal , Aortic Aneurysm, Abdominal/drug therapy , Disease Models, Animal , Humans , Muscle, Smooth, Vascular/metabolism , Oxidative Stress
3.
J. bras. nefrol ; 38(2): 153-160, graf
Article in Portuguese | LILACS | ID: lil-787878

ABSTRACT

RESUMO Introdução: p-cresol (PC) e p-cresil sulfato (PCS) são responsáveis por muitas das consequências clínicas uremia, tais como a aterosclerose em pacientes com Doença Renal Crônica (DRC). Objetivos: No presente trabalho, investigamos in vitro o impacto de PC e PCS na expressão da quimiocina monocyte chemoattractant protein-1 (MCP-1) via NF-kappa B (NF-κB) p65 em VSMC. Métodos: O PCS foi sintetizado por sulfatação do PC. As VSMC foram extraídas por digestão enzimática da veia do cordão umbilical e caracterizadas por imunofluorescência através do anticorpo α-actina. As células foram tratadas com PC e PCS em suas concentrações normal (n), urêmica (u) e urêmica máxima (m). A viabilidade celular foi avaliada pelo ensaio de MTT. A expressão de MCP-1 foi investigada por ELISA em sobrenadantes de células após o tratamento com as toxinas, com ou sem o inibidor de NF-κB p65. Resultados: Não houve diferença significativa na viabilidade das células após o tratamento com toxinas para todas as concentrações testadas. Houve um aumento significativo na expressão de MCP-1 em células tratadas com PCu e PCm (p < 0,001) e PCSn, PCSu e PCSm (p < 0,001), em comparação com o controle. Quando as VSMC foram tratadas com o inibidor de NF-κB p65 mais PCu e PCm, houve uma diminuição significativa na produção de MCP-1 (p < 0,005). Este efeito não foi observado com PCS. Conclusões: VSMC estão envolvidas na formação da lesão aterosclerótica e produção de MCP-1, o que contribui para o início da resposta inflamatória. Os nossos resultados sugerem que a PC medeia a produção de MCP-1 em VSMC, provavelmente através da via NF-κB p65 e que PCS atue através de uma subunidade diferente da via, uma vez que o inibidor da porção p65 não foi capaz de inibir a produção de MCP-1.


ABSTRACT Introduction: p-cresol (PC) and p-cresyl sulfate (PCS) are responsible for many of the uremia clinical consequences, such as atherosclerosis in Chronic Kidney Disease (CKD) patients. Objectives: We investigate the in vitro impact of PC and PCS on monocyte chemoattractant protein-1 (MCP-1) expression via NF-kappa B (NF-κB) p65 in VSMC. Methods: PCS was synthesized by PC sulfatation. VSMC were extracted by enzymatic digestion of umbilical cord vein and characterized by immunofluorescence against α-actin antibody. The cells were treated with PC and PCS at their normal (n), uremic (u) and maximum uremic concentrations (m). Cell viability was assessed by MTT. MCP-1 expression was investigated by ELISA in cells supernatants after toxins treatment with or without the NF-κB p65 inhibitor. Results: There was no significant difference in cell viability after toxins treatment for all concentrations tested. There was a significant increase in MCP-1 expression in cells treated with PCu and PCm (p < 0.001) and PCSn, PCSu and PCSm (p < 0.001), compared with the control. When VSMC were treated with the NF-κB p65 inhibitor plus PCu and PCm, there was a significant decrease in MCP-1 production (p < 0.005). This effect was not observed with PCS. Conclusions: VSMC are involved in atherosclerosis lesion formation and production of MCP-1, which contributes to the inflammatory response initiation. Our results suggest that PC mediates MCP-1 production in VSMC, probably through NF-κB p65 pathway, although we hypothesize that PCS acts through a different subunit pathway since NF-κB p65 inhibitor was not able to inhibit MCP-1 production.


Subject(s)
Humans , Sulfuric Acid Esters/pharmacology , Chemokine CCL2/biosynthesis , Chemokine CCL2/drug effects , Cresols/pharmacology , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Cells, Cultured , Transcription Factor RelA/physiology
4.
Acta cir. bras ; 31(3): 161-167, Mar. 2016. graf
Article in English | LILACS | ID: lil-777093

ABSTRACT

ABSTRACT PURPOSE: To develop an ex vivo model for the analysis of macroscopic, histological and immunohistochemical changes after experimental endovenous laser ablation (EVLA) of the great saphenous vein (GSV). METHODS: We describe a model produced with glass tubes and introducer sheaths to mimic the physiological conditions of EVLA procedures, such as tumescence and blood flow. A pilot study was conducted to evaluate an ex vivo procedure of EVLA of an incompetent GSV segment using a 1470-nm radial fiber diode laser (7 W power) and an automatic pull-back device. The vein segment was analyzed macroscopically and by hematoxylin & eosin staining, elastic fiber histochemistry, Gomori's trichrome staining, and alpha-smooth muscle actin immunohistochemistry. RESULTS: No perforations were observed macroscopically. No muscle cell adhesion was observed in the central part of the ablated vein, showing tissue disruption. There was low labeling for elastic fibers, disruption of muscle fibers, and a reduced expression of the specific marker for this cell type. CONCLUSION: This ex vivo endovenous laser ablation model is a low cost alternative to in vivo experiments, providing standardized experimental conditions.


Subject(s)
Humans , Saphenous Vein/surgery , Laser Therapy/methods , Lasers, Semiconductor/therapeutic use , Muscle, Smooth, Vascular/metabolism , Saphenous Vein/metabolism , Saphenous Vein/pathology , Varicose Veins/surgery , Varicose Veins/metabolism , Varicose Veins/pathology , Pilot Projects , Reproducibility of Results , Treatment Outcome , Models, Biological
5.
Rev. panam. salud pública ; 38(6): 450-456, nov.-dic. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-788102

ABSTRACT

OBJETIVO:Investigar el patrón de distribución espacial de la tasa de homicidios y su relación con las características sociodemográficas en las delegaciones de Benito Juárez, Coyoacán y Cuauhtémoc de la Ciudad de México en el año 2010. MÉTODOS: Estudio inferencial de corte transversal que usa métodos de análisis espacial para estudiar la asociación espacial de la tasa de homicidios y las características demográficas. La asociación espacial fue determinada a través del cociente de localización, análisis de regresión múltiple y el uso de la regresión geográficamente ponderada. RESULTADOS: Los homicidios muestran un patrón de localización heterogéneo con altas tasas en zonas con uso del suelo no residencial, con baja densidad de población y baja marginación. CONCLUSIONES: El uso de herramientas de análisis espacial son instrumentos poderosos para el diseño de políticas de seguridad pública preventiva y recreativa que busquen reducir la mortalidad por causas externas como homicidios.


OBJECTIVE:Investigate the spatial distribution pattern of the homicide rate and its relation to sociodemographic features in the Benito Juárez, Coyoacán, and Cuauhtémoc districts of Mexico City in 2010. METHODS: Inferential cross-sectional study that uses spatial analysis methods to study the spatial association of the homicide rate and demographic features. Spatial association was determined through the location quotient, multiple regression analysis, and the use of geographically weighted regression. RESULTS: Homicides show a heterogeneous location pattern with high rates in areas with non-residential land use, low population density, and low marginalization. CONCLUSIONS: Spatial analysis tools are powerful instruments for the design of prevention- and recreation-focused public safety policies that aim to reduce mortality from external causes such as homicides.


Subject(s)
Animals , Cattle , Female , Humans , Male , Rats , Hypoxia/metabolism , Cation Transport Proteins/metabolism , Hypertension, Pulmonary/metabolism , Muscle, Smooth, Vascular/metabolism , Animals, Congenic , Hypoxia/genetics , Arterioles/metabolism , Cell Hypoxia , Cell Proliferation , Cells, Cultured , Chronic Disease , Cation Transport Proteins/deficiency , Cation Transport Proteins/genetics , Chromosomes, Mammalian/genetics , Gene Knockdown Techniques , Homeostasis , Hypertension, Pulmonary/genetics , Intracellular Space/metabolism , Muscle, Smooth, Vascular/cytology , Rats, Inbred WKY , Zinc/metabolism
6.
Rev. bras. cir. cardiovasc ; 30(6): 644-649, Nov.-Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-774551

ABSTRACT

ABSTRACT α-smooth muscle actin, encoded by ACTA2 gene, is an isoform of the vascular smooth muscle actins, typically expressed in the vascular smooth muscle cells contributing to vascular motility and contraction. ACTA2 gene mutations cause a diversity of diffuse vasculopathies such as thoracic aortic aneurysms and dissections as well as occlusive vascular diseases, including premature coronary artery disease and ischemic stroke. Dynamics of differentiation-specific α-smooth muscle actin in arterial smooth muscle cells and proliferation of the proteins have been well described. Although a variety of research works have been undertaken in terms of modifications of α-smooth muscle actin and mutations of ACTA2 gene and myosin, the underlying mechanisms towards the pathological processes by way of gene mutations are yet to be clarified. The purpose of the present article is to describe the phenotypes of α-smooth muscle actin and implications of ACTA2 mutations in vasculopathies in order to enhance the understanding of potential mechanisms of aortic and coronary disorders.


Subject(s)
Humans , Actins/genetics , Aortic Diseases/metabolism , Coronary Disease/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Actins/metabolism , Aortic Diseases/genetics , Coronary Disease/genetics , Gene Expression , Muscle Contraction/physiology , Mutation/genetics , Phenotype
8.
Braz. j. med. biol. res ; 47(10): 826-833, 10/2014. graf
Article in English | LILACS | ID: lil-722174

ABSTRACT

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.


Subject(s)
Animals , Male , Muscle, Smooth, Vascular/physiology , Myosin Light Chains/metabolism , Protein Processing, Post-Translational/physiology , Vasoconstriction/physiology , Aorta, Thoracic , Acetylglucosamine/analogs & derivatives , Acetylglucosamine/pharmacology , Acylation/drug effects , Acylation/physiology , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Azepines/pharmacology , Blotting, Western , Enzyme Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Myosin-Light-Chain Kinase/metabolism , Myosin-Light-Chain Phosphatase/metabolism , Oxazoles/pharmacology , Oximes/pharmacology , Phenylcarbamates/pharmacology , Phenylephrine/agonists , Phosphorylation/drug effects , Phosphorylation/physiology , Rats, Wistar , Ribonucleotides/pharmacology , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , beta-N-Acetylhexosaminidases/antagonists & inhibitors
9.
Braz. j. med. biol. res ; 47(9): 789-798, 09/2014. graf
Article in English | LILACS | ID: lil-719317

ABSTRACT

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.


Subject(s)
Animals , Male , Aorta, Thoracic/physiopathology , Aortic Coarctation/physiopathology , Calcium/metabolism , Endothelium, Vascular/physiology , Muscle, Smooth, Vascular/physiopathology , Protein Kinase C/antagonists & inhibitors , Vasoconstriction/physiology , Angiotensin I/analysis , Angiotensin II/analysis , Aorta, Thoracic/injuries , Aorta, Thoracic/surgery , Blotting, Western , Blood Pressure/physiology , Chromatography, High Pressure Liquid , Endothelium, Vascular/injuries , Muscle, Smooth, Vascular/metabolism , Neuromuscular Depolarizing Agents/pharmacology , Phenylephrine/pharmacology , Potassium/pharmacology , Protein Kinase C/metabolism , Radioimmunoassay , Rats, Wistar , /metabolism , Vasoconstriction/drug effects
10.
Braz. j. med. biol. res ; 46(7): 574-579, ago. 2013. tab, graf
Article in English | LILACS | ID: lil-682398

ABSTRACT

Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40±2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca2+ were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca2+ at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) and Ca2+ (from 0.515±0.043 to 0.646±0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca2+ at various concentrations in the shock+drainage group (from 0.744±0.187 to 0.570±0.143 g/mg in Emax for NE and from 0.729±0.037 to 0.645±0.056 g/mg in Emax for Ca2+, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.


Subject(s)
Animals , Male , Calcium/metabolism , Lymph/physiology , Mesenteric Artery, Superior/physiopathology , Muscle, Smooth, Vascular/physiopathology , Myosin-Light-Chain Kinase/physiology , Shock, Hemorrhagic/physiopathology , Muscle Contraction , Mesenteric Artery, Superior/metabolism , Muscle, Smooth, Vascular/metabolism , Myosin Light Chains/metabolism , Myosin-Light-Chain Kinase/analysis , Random Allocation , Rats, Wistar , Shock, Hemorrhagic/enzymology
11.
Article in English | WPRIM | ID: wpr-152459

ABSTRACT

Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARgamma.


Subject(s)
Animals , Aorta/injuries , Calcium-Binding Proteins/genetics , Cell Proliferation , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/genetics , Hyperplasia/metabolism , Microfilament Proteins/genetics , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/drug effects , Nitric Oxide/metabolism , PPAR gamma/agonists , Promoter Regions, Genetic , Rats , Rats, Sprague-Dawley , Sp1 Transcription Factor/metabolism , Thiazolidinediones/pharmacology , Thrombospondins/genetics , Tunica Intima/metabolism , Vascular System Injuries/metabolism
12.
Braz. j. med. biol. res ; 44(9): 947-957, Sept. 2011. ilus
Article in English | LILACS | ID: lil-599673

ABSTRACT

During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.


Subject(s)
Animals , Humans , Rats , Endothelial Cells/metabolism , Nitric Oxide Donors/metabolism , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide/biosynthesis , Ruthenium Compounds/metabolism , Endothelium, Vascular/metabolism , Hypertension/physiopathology , Muscle, Smooth, Vascular/metabolism , Nitric Oxide/pharmacology , Vasodilation/physiology
13.
Braz. j. med. biol. res ; 41(6): 439-445, June 2008.
Article in English | LILACS | ID: lil-485854

ABSTRACT

Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo) and those occurring within the intracellular space (pHi), although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent), prostacyclin (PGI2/cAMP-dependent) and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.


Subject(s)
Animals , Humans , Acid-Base Equilibrium/physiology , Blood Vessels/physiopathology , Endothelium, Vascular/physiopathology , Muscle, Smooth, Vascular/physiopathology , Vasodilation/physiology , Acidosis/metabolism , Acidosis/physiopathology , Alkalosis/metabolism , Alkalosis/physiopathology , Epoprostenol/physiology , Hydrogen-Ion Concentration , Muscle, Smooth, Vascular/metabolism , Nitric Oxide/physiology
14.
Rev. argent. cardiol ; 75(2): 137-144, mar.-abr. 2007. tab, graf
Article in Spanish | LILACS | ID: lil-521634

ABSTRACT

En la remodelación arterial, como en otros tejidos del organismo, la matriz extracelular cumple un papel importante. La complejidad en la constitución de la matriz hace de la remodelación un fenómeno difícil de reproducir experimentalmente. En el caso de las arterias es clave la modificación de la relación músculo liso-matriz que produzca el cambio en el músculo liso del fenotipo contráctil al secretor. Para que ocurran los cambios en la matriz y en el músculo liso es determinante la activación de los genes productores de las proteasas que modificarán las relaciones célula-célula y célula-matriz.


Subject(s)
Muscle, Smooth, Vascular , Extracellular Matrix/metabolism , Matrix Metalloproteinases/metabolism , Muscle, Smooth, Vascular/metabolism , Arteries
15.
Biol. Res ; 37(4): 641-645, 2004. ilus, graf
Article in English | LILACS | ID: lil-437520

ABSTRACT

A capacitative Ca2+ entry (CCE) pathway, activated by depletion of intracellular Ca2+ stores, is thought to mediate much of the Ca2+ entry evoked by receptors that stimulate phospholipase C (PLC). However, in A7r5 vascular smooth muscle cells, vasopressin, which stimulates PLC, empties intracellular Ca2+ stores but simultaneously inhibits their ability to activate CCE. The diacylglycerol produced with the IP3 that empties the stores is metabolized to arachidonic and this leads to activation of nitric oxide (NO) synthase, production of NO and cyclic GMP, and consequent activation of protein kinase G. The latter inhibits CCE. In parallel, NO directly activates a non-capacitative Ca2+ entry (NCCE) pathway, which is entirely responsible for the Ca2+ entry that occurs in the presence of vasopressin. This reciprocal regulation of two Ca2+ entry pathways ensures that there is sequential activation of first NCCE in the presence of vasopressin, and then a transient activation of CCE when vasopressin is removed. We suggest that the two routes for Ca2+ entry may selectively direct Ca2+ to processes that mediate activation and then recovery of the cell.


Subject(s)
Animals , Calcium/metabolism , Calcium Channels/metabolism , Type C Phospholipases/metabolism , Muscle, Smooth, Vascular/metabolism , Calcium Signaling/physiology , Vasopressins/metabolism , Cell Line , Cyclic GMP/metabolism , Nitric Oxide/biosynthesis
16.
Article in English | WPRIM | ID: wpr-634186

ABSTRACT

The effects of 3, 4-Dihydroxyacetophenone (3, 4-DHAP) on cytosolic free calcium [Ca2+]i in pulmonary artery endothelia (PAECs) and smooth muscle cells (PASMCs) during acute hypoxia were studied. Porcine pulmonary artery endothelial and smooth muscle cells (PASMCs) were cultured primarily, and they were divided into 4 groups: groups incubated under normoxia or hypoxia and those with or without treatment with 3,4-DHAP. The [Ca2+]i of both PAECs and PASMCs was measured by determining the fluorescence of fura 2 AM on spetrofluorometer. Our results showed that hypoxia caused significant elevation of [Ca2+]i, in both PAECs and PASMCs, 3,4-DHAP could attenuate the hypoxic elevation of [Ca2+]i only in PASMCs but not in PAECs. It is concluded that 3,4-DHAP decreases the hypoxic elevation of [Ca2+]i in PASMCs. This might contribute to its inhibitory effect on hypoxic pulmonary vasoconstriction.


Subject(s)
Acetophenones/pharmacology , Calcium/metabolism , Cell Hypoxia , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Pulmonary Artery/cytology , Pulmonary Artery/metabolism , Swine
17.
Biocell ; 27(2): 189-196, Aug. 2003.
Article in English | LILACS | ID: lil-384244

ABSTRACT

Remodeling of large and small arteries contributes to the development and complications of hypertension. Artery structural changes in chronic sustained hypertension include vascular smooth muscle cells (VSMC) proliferation and extracellular matrix (ECM) modifications. Extracellular constituents such as proteoglycans (PGs), may modulate vascular stiffness and VSMC growth and differentiation. We examined the effect of growth factors on secreted and membrane-bound PGs synthesis by cultured aortic smooth muscle cells (SMC) from 12- to 14- week-old spontaneously hypertensive rats (SHR) and age-matched Wistar rats. After stimulation with platelet-derived growth factor (PDGF-BB), 10% fetal calf serum (FCS) or 0.1% FCS as control, PGs synthesis (dpm/ng DNA) was evaluated in the medium (M-ECM) and in the cell layer (P-ECM) by a double-isotopic label method using both [3H]-glucosamine and [35S]-sodium sulfate which are incorporated into all complex carbohydrates or only into sulfated dysaccharides, respectively. Data are presented as percent of the control (0.1% FCS). SHR VSMC displayed a significantly greater synthesis of M-ECM [3H]-PGs than Wistar rat cells, with both treatments, but no differences in M-ECM [35S] uptake were found in any case. In the P-ECM, both PDGF-BB and 10% FCS produced a greater effect on [3H]-PGs and sulfated PGs synthesis in VSMC from SHR. An important change seen in SHR cells was a significant decreased sulfation, assessed by [35S]/[3H] ratio, in basal and stimulation conditions. Present results indicate the existence of changes in PGS synthesis and modulation in VSMC from a conduit-artery of SHR and support the pathophysiological role proposed for matrix proteoglycans in the vascular wall changes associated to hypertension and related vascular diseases as atherosclerosis.


Subject(s)
Male , Aorta/metabolism , Hypertension/metabolism , Hypertrophy/metabolism , Extracellular Matrix/metabolism , Muscle, Smooth, Vascular/metabolism , Proteoglycans/metabolism , Aorta/cytology , Arteriosclerosis/metabolism , Arteriosclerosis/pathology , Arteriosclerosis/physiopathology , Cells, Cultured , Cell Division/drug effects , Cell Division/physiology , Platelet-Derived Growth Factor/metabolism , Platelet-Derived Growth Factor/pharmacology , Glucosamine/metabolism , Extracellular Matrix/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular , Proteoglycans/drug effects , Proteoglycans , Rats , Rats, Inbred SHR , Sulfur Radioisotopes , Sulfates/metabolism
18.
Article in English | IMSEAR | ID: sea-85292

ABSTRACT

Homocysteine has been recently recognised as a risk factor for atherosclerotic vascular disease. Numerous studies have studied adverse influence of homocysteine on endothelial cells, vascular smooth muscle cells, connective tissue, interactions with plasma lipoproteins, clotting factors and platelets. It has been suggested that endothelial damage is mediated by hydrogen peroxide, a by-product of auto-oxidation of homocysteine. Human studies have shown that high levels of homocysteine are associated with impaired endothelial dependent vasodilatation in healthy subjects indicating that the bio-availability of nitric oxide (NO) is decreased in those with hyper-homocysteinemia. Homocysteine thialactone (a by-product of homocysteine auto-oxidation) combines with native LDL to form oxidized LDL which is taken up by intimal macrophages to form foam cells which is the beginning of atheromatous plaques. Homocysteine has also influence on proliferation of vascular smooth muscle cells and collagen deposition in atheromatous plaque. In addition several retrospective and prospective studies have shown that hyperhomocysteinaemia is associated with atheromatous and vascular events. Observations in 80 clinical and epidemiological studies have indicated that hyper-homocysteinaemia is a risk factor for atherosclerotic disease. However there are some studies which conclude that homocysteine is not a major risk factor for coronary heart disease.


Subject(s)
Arteriosclerosis/etiology , Clinical Trials as Topic , Endothelium, Vascular/metabolism , Homocysteine/metabolism , Humans , Hyperhomocysteinemia/complications , Hypertension/etiology , Muscle, Smooth, Vascular/metabolism , Risk Factors
19.
Braz. j. med. biol. res ; 34(4): 549-52, Apr. 2001. graf
Article in English | LILACS | ID: lil-282622

ABSTRACT

Nitric oxide (NO)-synthase is present in diaphragm, phrenic nerve and vascular smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg) at the presynaptic level increases the amplitude of muscular contraction (AMC) and induces tetanic fade when the muscle is indirectly stimulated at low and high frequencies, respectively. However, the precursor in muscle reduces AMC and maximal tetanic fade when the preparations are stimulated directly. In the present study the importance of NO synthesized in different tissues for the L-Arg-induced neuromuscular effects was investigated. Hemoglobin (50 nM) did not produce any neuromuscular effect, but antagonized the increase in AMC and tetanic fade induced by L-Arg (9.4 mM) in rat phrenic nerve-diaphragm preparations. D-Arg (9.4 mM) did not produce any effect when preparations were stimulated indirectly at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the reduction in maximal tetanic tension induced by L-Arg in preparations previously paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic effects induced by L-Arg were antagonized by hemoglobin, the present results suggest that NO synthesized in muscle acts on nerve and skeletal muscle. Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to act on skeletal muscle


Subject(s)
Animals , Male , Female , Rats , Arginine/antagonists & inhibitors , Hemoglobins/pharmacology , Muscle Contraction/drug effects , Nitric Oxide/antagonists & inhibitors , Arginine/pharmacology , Diaphragm/drug effects , Diaphragm/metabolism , Electric Stimulation , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Nitric Oxide/biosynthesis , Nitric Oxide/pharmacology , Phrenic Nerve/drug effects , Phrenic Nerve/metabolism , Rats, Wistar
20.
Indian J Physiol Pharmacol ; 1999 Jul; 43(3): 389-92
Article in English | IMSEAR | ID: sea-107972

ABSTRACT

The activity of receptor-operated Ca2+ channels (ROCCs) was studied in rat portal vein in L-thyroxine-induced experimental hyperthyroidism. The following parameters were evaluated: 1. NE-stimulated 45Ca influx. 2. CaCl2-induced contractile responses in Ca2+ free NE-stimulated tissues to calculate EC50 value of CaCl2. The NE (10(-6)mol) stimulated 45Ca influx and the mean EC50 value of CaCl2 did not differ significantly in portal veins isolated from hyperthyroid rats as compared to those of euthyroid control rats. The study revealed no significant change in the functional status of ROCCs in experimental hyperthyroidism.


Subject(s)
Animals , Calcium Channels/metabolism , Calcium Signaling , Hyperthyroidism/chemically induced , Male , Muscle, Smooth, Vascular/metabolism , Portal Vein/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha/metabolism , Thyroxine/toxicity
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