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1.
Chin J Physiol ; 57(5): 238-48, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25241983

RESUMO

Intracellular pH (pHi) is a critical factor influencing many important cellular functions. Acid extrusion carriers such as an Na⁺/H⁺ exchanger (NHE) Na⁺/HCO3⁻ cotransporter (NBC) and monocarboxylate transporters (MCT) can be activated when cells are in an acidic condition (pHi < 7.1). Human radial artery smooth muscle cells (HRASMC) is an important conduit in coronary artery bypass graft surgery. However, such far, the pHi regulators have not been characterized in HRASMCs. We therefore investigated the mechanism of pHi recovery from intracellular acidosis and alkalosis, induced by NH4Cl-prepulse and Na-acetate-prepulse, respectively, using intracellular 2',7'-bis(2-carboxethyl)-5(6)- carboxy-fluorescein (BCECF)-fluorescence in HRASMCs. Cultured HRASMCs were derived from the segments of human radial artery that were obtained from patients undergoing bypass grafting. The resting pHi is 7.22 ± 0.03 and 7.17 ± 0.02 for HEPES- (nominally HCO3⁻-free) and CO2/HCO3⁻- buffered solution, respectively. In HEPES-buffered solution, a pHi recovery from induced intracellular acidosis could be blocked completely by 30 µM HOE 694 (3-methylsulfonyl-4-piperidinobenzoyl, guanidine hydrochloride) a specific NHE inhibitor, or by removing [Na⁺]0. In 3% CO2/HCO3⁻-buffered solution, HOE 694 slowed the pHi recovery from the induced intracellular acidosis only, while adding together with DIDS (a specific NBC inhibitor) or removal of [Na⁺]0 entirely inhibited the acid extrusion. Moreover, α-cyano-4-hydroxycinnamate (CHC; a specific blocker of MCT) blocked the lactate-induced pHi changes. In conclusion, we demonstrate, for the first time, that 3 different pHi regulators responsible for acid extruding, i.e. NHE and NBC, and MCT, are functionally co-existed in cultured HRASMCs.


Assuntos
Equilíbrio Ácido-Base/fisiologia , Ácidos/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Miócitos de Músculo Liso/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Simportadores/metabolismo , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Equilíbrio Ácido-Base/efeitos dos fármacos , Acidose/metabolismo , Proteínas de Transporte de Cátions/antagonistas & inibidores , Ácidos Cumáricos/farmacologia , Guanidinas/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Modelos Biológicos , Transportadores de Ácidos Monocarboxílicos/efeitos adversos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Cultura Primária de Células , Artéria Radial/citologia , Simportadores de Sódio-Bicarbonato/antagonistas & inibidores , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Sulfonas/farmacologia , Simportadores/efeitos adversos
2.
Ann Thorac Surg ; 98(5): 1875-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25258159

RESUMO

Since its reintroduction in the early 1990s the radial artery has gained a major role in coronary surgery, currently representing a valid alternative to the right internal thoracic artery as a second arterial graft. However, its peculiar morphologic and functional features have both surgical and clinical critical implications that must be taken into account. In this review we summarize the current totality of evidence on the biologic characteristics of the radial artery, such as its histopathology, vasoreactivity, and remodeling, and discuss their potential implications for use as a coronary bypass conduit.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Artéria Radial , Resistência Vascular/fisiologia , Humanos , Artéria Radial/citologia , Artéria Radial/fisiologia , Artéria Radial/transplante
3.
Zhonghua Nei Ke Za Zhi ; 52(6): 464-8, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24059991

RESUMO

OBJECTIVE: To investigate whether inflammation exacerbates lipid accumulation in the radial arteries of patients with end-stage renal disease (ESRD) and to explore its underlying mechanisms. METHODS: Thirty ESRD patients receiving arteriovenostomy were included. The patients were divided by the plasma level of C-reactive protein into control group (n = 16) and inflamed group (n = 14). Foam cell formation and lipid droplet accumulation were checked by HE staining and Oil red O staining. Tissue inflammation and intracellular cholesterol trafficking correlated proteins were examined by immunohistochemistry or immunofluorescent staining. RESULTS: There were no differences in primary diseases, age, body weight, hemoglobin, total protein, albumin, glucose, lipid profile between the two groups (all P values >0.05). The expressions of tumor necrosis factor α (TNFα) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. There was significant lipid accumulation in the radial arteries of inflamed group compared to the control group, which was correlated with the increased protein expressions of low density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP cleavage-activating protein (SCAP). Confocal microscopy observation showed that inflammation enhanced the translocation of SCAP escorting SREBP-2 from endoplasmic reticulum to Golgi, thereby activating LDLr gene transcription. Further analysis showed that dysregulation of LDLr pathway induced by inflammation was associated with increased protein expression of mTOR (r = 0.733, P < 0.05), especially with the enhanced co-expression of mTOR and SREBP-2(P < 0.05). CONCLUSION: Inflammation accelerates the progression of foam cell formation in ESRD patients via dysregulation of LDLr pathway, which might be partly through the activation of mTOR pathway.


Assuntos
Células Espumosas/citologia , Inflamação , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Receptores de LDL/metabolismo , Adulto , Idoso , Proteína C-Reativa/metabolismo , Quimiocina CCL2/metabolismo , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/citologia , Artéria Radial/patologia , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
PLoS One ; 7(5): e36482, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22574168

RESUMO

In hemodialysis patients, a native arteriovenous fistula (AVF) is the preferred form of permanent vascular access. Despite recent improvements, vascular access dysfunction remains an important cause of morbidity in these patients. In this prospective observational cohort study, we evaluated potential risk factors for native AVF dysfunction. We included 68 patients with chronic renal disease stage 5 eligible for AVF construction at the Department of General and Vascular Surgery, Central Clinical Hospital Ministry of Internal Affairs, Warsaw, Poland. Patient characteristics and biochemical parameters associated with increased risk for AVF failure were identified using Cox proportional hazards models. Vessel biopsies were analyzed for inflammatory cells and potential associations with biochemical parameters. In multivariable analysis, independent predictors of AVF dysfunction were the number of white blood cells (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.24 to 2.25; p<0.001), monocyte number (HR 0.02; 95% CI 0.00 to 0.21; p = 0.001), and red blood cell distribution width (RDW) (HR 1.44; 95% CI 1.17 to 1.78; p<0.001). RDW was the only significant factor in receiver operating characteristic curve analysis (area under the curve 0.644; CI 0.51 to 0.76; p = 0.046). RDW>16.2% was associated with a significantly reduced AVF patency frequency 24 months after surgery. Immunohistochemical analysis revealed CD45-positive cells in the artery/vein of 39% of patients and CD68-positive cells in 37%. Patients with CD68-positive cells in the vessels had significantly higher white blood cell count. We conclude that RDW, a readily available laboratory value, is a novel prognostic marker for AVF failure. Further studies are warranted to establish the mechanistic link between high RDW and AVF failure.


Assuntos
Fístula Arteriovenosa/sangue , Fístula Arteriovenosa/cirurgia , Contagem de Eritrócitos , Diálise Renal/métodos , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Coortes , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Estudos Prospectivos , Artéria Radial/citologia , Artéria Radial/cirurgia , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Veias/citologia , Veias/cirurgia
5.
Zhonghua Wai Ke Za Zhi ; 49(12): 1128-31, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22333457

RESUMO

OBJECTIVE: To compare the differences in nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization between human radial artery (RA) and saphenous vein (SV) through direct measurement of NO and membrane potential. METHODS: RA (n = 8), SV (n = 23), and surgical prepared SV (PV, n = 9, dilatation with normal saline solution at a pressure of 100 - 600 mmHg, 1 mmHg = 0.133 kPa) segments (5 mm long) taken from patients undergoing coronary artery bypass grafting were placed in an organ chamber. The NO-sensitive electrode and intracellular glass microelectrode was used to directly measure the NO release and the membrane potential changes in response to acetylcholine (ACh) and bradykinin (BK) before and after incubation with NG-nitro-L-arginine, indomethacin, and oxyhemoglobin. RESULTS: The basal release of NO in RA [(11.9 ± 1.8) nmol/L] was significantly greater than that in SV [(9.9 ± 2.8) nmol/L, P = 0.041]. BK-induced NO release in RA was lower than that in SV [for BK 10(-7) mol/L: (25.8 ± 3.6) nmol/L vs. (43.7 ± 8.2) nmol/L, P = 0.006]. Both basal and ACh- or BK-induced NO release in PV were significantly reduced [basal release: PV (3.4 ± 1.4) nmol/L; P = 0.006 vs. RA; P = 0.002 vs. SV; stimulated release: for ACh 10(-5) mol/L: PV (4.8 ± 3.2) nmol/L; vs. RA (28.6 ± 7.9) nmol/L, P = 0.005; vs. SV (27.4 ± 3.7) nmol/L, P = 0.003; for BK 10(-7) mol/L: PV (7.0 ± 3.6) nmol/L; vs. RA (25.8 ± 3.6) nmol/L, P = 0.016; vs. SV (43.7 ± 8.2) nmol/L, P = 0.004]. EDHF-mediated hyperpolarization was greater in RA than that in SV [ACh 10(-5) mol/L: (-9.7 ± 1.9) mV vs. (-4.5 ± 1.1) mV, n = 17, P = 0.002]. CONCLUSIONS: RA is superior to SV in terms of NO basal release and EDHF-mediated endothelial function. Surgical preparation and pressure dilatation may severely impair the NO-mediated endothelial function of SV, which may contribute to the poor long-term patency of SV coronary graft.


Assuntos
Fatores Biológicos/metabolismo , Células Endoteliais/metabolismo , Óxido Nítrico/metabolismo , Células Endoteliais/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Humanos , Masculino , Potenciais da Membrana/fisiologia , Pessoa de Meia-Idade , Artéria Radial/citologia , Veia Safena/citologia
6.
Rev. bras. cardiol. invasiva ; 18(2): 177-184, jun. 2010.
Artigo em Português | LILACS | ID: lil-559924

RESUMO

Introdução: A via radial é objeto de interesse crescente para procedimentos diagnósticos e terapêuticos por possuir diversas vantagens, entre as quais comodidade para o paciente no pós-procedimento imediato, com retorno precoce a suas atividades, diminuição do tempo de internação, com consequente redução dos custos hospitalares, e baixo índice de complicação do sítio de punção comparativamente à via femoral, reduzindo a taxa de sangramento maior, que, por sua vez, está relacionada ao aumento do risco de morte e eventos isquêmicos. Método: Análise retrospectiva de 1.807 pacientes consecutivos submetidos a angioplastia coronária percutânea (ATC) off-label entre setembro de 2006 e dezembro de 2009. Comparamos os pacientes submetidos a ATC pelas vias radial e femoral em relação às evoluções hospitalar e tardia. Resultados: Predominaram na via radial pacientes mais jovens, do sexo masculino, com menor complexidade angiográfica, fato que se deveu à curva de aprendizado. Houve menor taxa de eventos cardíacos adversos maiores (ECAM), óbito e revascularização do vasoalvo na via radial, tanto na fase hospitalar como na fase tardia, em virtude do perfil clínico-angiográfico mais favorável. A via femoral foi preditor independente de ECAM hospitalar. A curva de sobrevivência ajustada, no entanto, mostrou que a via de acesso não teve influência significativa nos eventos clínicos a longo prazo. Conclusão: A técnica radial é segura na abordagem de pacientes selecionados com indicação off-label, apresentando resultados clínicos satisfatórios nas evoluções inicial e tardia.


Background: There is increasing interest in the use of the radial approach in diagnostic and therapeutic proceduresdue to several advantages such as patient comfort in the immediate post-procedure with early return to daily routine activities, decreased hospitalization time and consequentreduction of hospital costs and low puncture site complication rates when compared with the femoral approach, reducing the rate of major bleeding, which is in turn related to increased risk of death and ischemic events. Method:Retrospective analysis of 1,807 consecutive patients undergoingoff-label percutaneous transluminal coronary angioplasty (PTCA) from September 2006 to December 2009.The outcome of patients undergoing PTCA using the radial and femoral approaches during hospitalization and late follow-up were compared. Results: The radial approach prevailed in younger, male patients with lower angiographic complexity, which was due to the learning curve. Major adverse cardiac events (MACE), death and target-vessel revascularization rates were lower when the radial approachwas used, both during hospitalization and in the late follow-up due to a more favorable clinical-angiographic profile.The femoral approach was an independent predictor of hospital MACE. The adjusted survival curve, however,showed that the access route did not have a significant impact on long-term clinical events. Conclusion: Thetransradial approach is safe when used in selected patients with off-label indication, providing good clinical results in the early and late follow-up.


Assuntos
Humanos , Angioplastia/enfermagem , Artéria Radial/citologia , Doença das Coronárias/diagnóstico
7.
Physiol Res ; 59(2): 187-194, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19537928

RESUMO

The aim of this study was to test the hypothesis that vasorelaxing action of vasonatrin peptide (VNP) is due to activation of the large-conductance Ca(2+)-activated potassium channel (BK(Ca)) via guanylyl cyclase (GC)-coupled natriuretic peptide receptors (NPRs) in vascular smooth muscle cells (VSMCs). Contraction experiments were performed using human radial artery, whereas BK(Ca) current by patch clamp was recorded in cells from rat mesenteric artery. Contractility of rings cut from human radial artery was detected in vitro. As a result, VNP induced a dose-dependent vasorelaxation of human radial artery, which could be mimicked by 8-Br-cGMP, and suppressed by TEA, a blocker of BK(Ca), HS-142-1, a blocker of GC-coupled NPRs, or methylene blue (MB), a selective inhibitor of guanylyl cyclase. Sequentially, whole-cell K(+) currents were recorded using patch clamp techniques. BK(Ca) current of VSMCs isolated from rat mesentery artery was obtained by subtracting the whole cell currents after applications of 10(-7) mol/l iberiotoxin (IBX) from before its applications. In accordance with the results of arterial tension detection, BK(Ca) current was significantly magnified by VNP, which could also be mimicked by 8-Br-cGMP, whereas suppressed by HS-142-1, or MB. Taken together, VNP acts as a potent vasodilator, and NPRA/B-cGMP-BK(Ca) is one possible signaling system involved in VNP induced relaxation.


Assuntos
Fator Natriurético Atrial/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/agonistas , Músculo Liso Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Fator Natriurético Atrial/fisiologia , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Relação Dose-Resposta a Droga , Guanilato Ciclase/fisiologia , Humanos , Técnicas In Vitro , Canais de Potássio Ativados por Cálcio de Condutância Alta/fisiologia , Artérias Mesentéricas/citologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Técnicas de Patch-Clamp , Peptídeos/farmacologia , Artéria Radial/citologia , Artéria Radial/efeitos dos fármacos , Artéria Radial/fisiologia , Ratos , Receptores do Fator Natriurético Atrial/fisiologia , Tetraetilamônio/farmacologia , Vasodilatação/fisiologia
8.
Eur J Histochem ; 52(1): 39-44, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18502721

RESUMO

A growing body of evidence suggests that the angiotensin II fragments, Ang(1-7) and Ang(3-8), have a vasoactive role, however ACE2, the enzyme that produces Ang(1-7), or AT4R, the receptor that binds Ang (3-8), have yet been simultaneously localised in both normal and diseased human conduit blood vessels. We sought to determine the immunohistochemical distribution of ACE2 and the AT4R in human internal mammary and radial arteries from patients undergoing coronary artery bypass surgery. We found that ACE2 positive cells were abundant in both normal and diseased vessels, being present in neo-intima and in media. ACE2 positive immunoreactivity was not present in the endothelial layer of the conduit vessels, but was clearly evident in small newly formed angiogenic vessels as well as the vaso vasorum. Endothelial AT4R immunoreactivity were rarely observed in either normal and diseased arteries, but AT4R positive cells were observed adjacent to the internal elastic lamine in the internal mammary artery, in the neo-intima of radial arteries, as well as in the media of both internal mammary artery and radial artery. AT4R was abundant in vaso vasorum and within small angiogenic vessels. Both AT4R and ACE2 co-localised with smooth muscle cell alpha actin. This study identifies smooth muscle cell alpha actin positive ACE2 and AT4R in human blood vessels as well as in angiogenic vessels, indicating a possible role for these enzymes in pathological disease.


Assuntos
Doença da Artéria Coronariana/metabolismo , Endotélio Vascular/química , Artéria Torácica Interna/química , Músculo Liso Vascular/química , Peptidil Dipeptidase A/análise , Artéria Radial/química , Receptores de Angiotensina/análise , Actinas/análise , Enzima de Conversão de Angiotensina 2 , Ponte de Artéria Coronária , Doença da Artéria Coronariana/enzimologia , Endotélio Vascular/enzimologia , Humanos , Artéria Torácica Interna/citologia , Artéria Torácica Interna/enzimologia , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/química , Miócitos de Músculo Liso/enzimologia , Artéria Radial/citologia , Artéria Radial/enzimologia
9.
J Thorac Cardiovasc Surg ; 131(3): 651-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16515919

RESUMO

OBJECTIVES: Late graft occlusions after coronary artery bypass grafting have been ascribed to neointimal hyperplasia. Given the pivotal role of smooth muscle cells in the pathogenesis of neointimal hyperplasia and the phenotypic heterogeneity of smooth muscle cells across vessels, we hypothesized that differences in long-term graft patency are at least partly related to differences in smooth muscle cell properties. The aim of the present study was to compare the vascular-wall remodeling of human internal thoracic artery, radial artery, and saphenous vein bypass conduits. METHODS: We evaluated the intimal thickening of the human graft segments in organ cultures (histopathology, morphometric, and immunofluorescence analyses) and assessed the properties of cultured smooth muscle cells isolated from these vessels in terms of cell proliferation (tritiated thymidine incorporation), migration (modified Boyden chamber), and collagen synthesis (tritiated proline incorporation). RESULTS: The total vessel-wall growth index and the intimal growth index were significantly higher for saphenous vein rings than for radial artery and internal thoracic artery rings. Immunofluorescence analyses showed predominant involvement of smooth muscle cells in neointimal growth induced by organ culture of saphenous vein rings. Cell proliferation was significantly higher in saphenous vein smooth muscle cells than in radial artery smooth muscle cells and significantly higher in radial artery smooth muscle cells than in internal thoracic artery smooth muscle cells. Migration of smooth muscle cells from saphenous vein grafts was significantly greater than from internal thoracic artery or radial artery grafts. Collagen synthesis was similar in smooth muscle cells from internal thoracic artery, radial artery, and saphenous vein grafts. CONCLUSIONS: Ex vivo vascular-wall remodeling and smooth muscle cell intrinsic growth and migratory properties are dissimilar between arterial and venous grafts and might shed light on reported angiographic patency rates of these grafts.


Assuntos
Artéria Torácica Interna/citologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Artéria Radial/citologia , Veia Safena/citologia , Túnica Íntima/citologia , Idoso , Células Cultivadas , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Técnicas de Cultura de Órgãos
10.
J Thorac Cardiovasc Surg ; 131(2): 388-94, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16434269

RESUMO

BACKGROUND: The radial artery's propensity for vasospasm and vulnerability to surgical trauma are well known. A less invasive endoscopic method to harvest the radial artery was recently introduced, but its effect on radial artery integrity is unknown. METHODS: To compare the effects of harvest method on radial artery function, we prospectively randomized 54 patients undergoing coronary artery bypass grafting with the radial artery into 3 groups on the basis of harvest techniques: endoscopic, conventional with cautery, and conventional with harmonic scalpel. We assessed endothelium-dependent and endothelium-independent relaxation of radial artery segments to sequential doses of acetylcholine and nitroglycerin, respectively, using standard organ-chamber methodology. Vasospasm was assessed as the vasoconstrictor response to the thromboxane analog U46619. We assessed endothelial integrity using light and electron microscopy and by rating intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and P-selectin expression by means of immunohistochemistry on a semiquantitative 0- to 3-point scale. Harvest procedures were performed by a single surgeon, and data analyses were blinded to the harvesting method. RESULTS: Maximal relaxation-contraction responses to acetylcholine, nitroglycerin, and U46619 and effective drug concentration yielding 50% response were similar in the 3 groups. Adhesion molecule expression and histologic changes, as assessed by means of light and electron microscopy, were similar in the 3 groups. CONCLUSIONS: Endoscopic harvest does not alter radial artery vasoreactivity or endothelial integrity compared with conventional harvest techniques. Because the endoscopic technique is less invasive, it might prove to be the technique of choice to harvest the radial artery.


Assuntos
Ponte de Artéria Coronária , Endoscopia , Artéria Radial/transplante , Coleta de Tecidos e Órgãos/métodos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Molécula 1 de Adesão Intercelular/análise , Masculino , Pessoa de Meia-Idade , Selectina-P/análise , Artéria Radial/citologia , Artéria Radial/efeitos dos fármacos , Artéria Radial/metabolismo , Molécula 1 de Adesão de Célula Vascular/análise , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia
11.
Circulation ; 107(20): 2548-50, 2003 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-12742988

RESUMO

BACKGROUND: The proliferation of vascular smooth muscle cells (VSMCs) is a known response to arterial injury that is an important part of the process of restenosis and atherosclerosis. People with diabetes have an increased risk of cardiovascular disease resulting from accelerated coronary atherosclerosis. The newest drugs for Type 2 diabetes are thiazolidinediones, which are insulin-sensitizing peroxisome proliferator activating receptor-gamma (PPARgamma) ligands. We investigated the antiproliferative effects of troglitazone, rosiglitazone, and pioglitazone on VSMCs derived from the three vascular beds used for coronary artery by-pass grafting: the internal mammary and radial artery and saphenous veins. METHODS AND RESULTS: The three vessels yielded proliferating cells of slightly differing morphology. Inhibition of cell proliferation was assessed by cell counting and cell cycle studies by Western blotting for phosphorylated retinoblastoma protein. All three thiazolidinediones showed inhibitory potency toward cell proliferation with a potency troglitazone>rosiglitazone approximately pioglitazone, and this potency profile was maintained toward the growth factor and insulin-stimulated phosphorylation of the retinoblastoma protein, which controls cell cycle progression. CONCLUSIONS: The inhibitory potency of clinical thiazolidinediones toward different vascular sources is dependent on the individual thiazolidinedione and very little on the vascular source.


Assuntos
Cromanos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Tiazóis/farmacologia , Tiazolidinedionas , Fatores de Transcrição/metabolismo , Becaplermina , Contagem de Células , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Cromanos/metabolismo , Relação Dose-Resposta a Droga , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Ligantes , Artéria Torácica Interna/citologia , Mitógenos/farmacologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Fosforilação/efeitos dos fármacos , Pioglitazona , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-sis , Artéria Radial/citologia , Proteína do Retinoblastoma/metabolismo , Rosiglitazona , Veia Safena/citologia , Tiazóis/metabolismo , Troglitazona
12.
Atherosclerosis ; 162(1): 55-61, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11947897

RESUMO

Expression levels of the purinergic P2X receptor subunits (P2X(1) to P2X(7)) and P2Y(2) were examined in the endothelial cell layer of internal mammary artery (Ann. Thorac. Surg. 54 (1992) 652), radial artery (Ann. Thorac. Surg. 16 (1973) 111) and saphenous vein (Ann. Thorac. Surg. 20 (1975) 628) samples obtained at surgery for coronary artery bypass grafts using immunohistochemistry and confocal microscopy. Similar levels of P2X(1), P2X(2), P2X(3), P2X(7) and P2Y(2) were found in the endothelial cells in all vessels examined while the levels of P2X(5) and P2X(6) were uniformly lower. A clear difference was measured in P2X(4) expression between arteries and veins. Both radial and internal mammary arteries exhibited very low levels of P2X(4) whereas the level in the saphenous vein was 14.6 fold higher (P<0.0001), approaching that of the major receptor subtypes. These data showing strong expression of P2X(4) in veins have implications for the choice of vessels used in coronary artery bypass grafts given that P2X(4) is involved in calcium influx into endothelial cells, modulates blood vessel contractility and is up-regulated in situations involving intima proliferation suggesting vein grafts are more susceptible to developing atherosclerosis.


Assuntos
Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Artéria Torácica Interna/citologia , Artéria Torácica Interna/metabolismo , Artéria Radial/citologia , Artéria Radial/metabolismo , Receptores Purinérgicos P2/biossíntese , Receptores Purinérgicos P2/sangue , Veia Safena/citologia , Veia Safena/metabolismo , Especificidade de Anticorpos/imunologia , Ponte de Artéria Coronária , Imunofluorescência , Humanos , Imuno-Histoquímica , Imunofenotipagem , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Receptores Purinérgicos P2/imunologia
13.
Am J Physiol Heart Circ Physiol ; 280(6): H2451-5, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11356597

RESUMO

In human radial arteries, a nitric oxide/prostanoid-independent mechanism that has the pharmacological characteristics of an EDHF contributes to endothelium-dependent relaxation. H2O2 can act as an EDHF in some vascular beds. We examined the hypothesis that endogenously produced H2O2 mediated the nitric oxide/prostanoid-independent relaxation to carbachol in radial arteries obtained from patients undergoing coronary artery bypass surgery. Superoxide levels, measured by chemiluminescence, were similar in radial and internal mammary arteries, but immunohistochemical staining for Cu/Zn superoxide dismutase (SOD) was lower in endothelium from radial arteries. In organ chamber studies, neither addition of catalase nor addition of SOD to the bathing fluid modified nitric oxide/prostanoid-independent relaxations to carbachol in radial arteries. However, nitric oxide-dependent vasorelaxation was enhanced in the presence of SOD. Thus the nitric oxide/prostanoid-independent relaxation to carbachol is not due to H2O2 and, unlike nitric oxide-mediated vasorelaxation, is not attenuated by superoxide. Blood vessels showing EDHF-mediated relaxations resistant to oxidative stress may provide favorable outcomes in revascularization surgery.


Assuntos
Fatores Biológicos , Peróxido de Hidrogênio/metabolismo , Artéria Radial/metabolismo , Fatores Biológicos/fisiologia , Carbacol/farmacologia , Catalase/farmacologia , Agonistas Colinérgicos/farmacologia , Relação Dose-Resposta a Droga , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Imuno-Histoquímica , Técnicas In Vitro , Artéria Torácica Interna/citologia , Artéria Torácica Interna/efeitos dos fármacos , Artéria Torácica Interna/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Perfusão , Artéria Radial/citologia , Artéria Radial/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Superóxidos/metabolismo , Vasodilatação/efeitos dos fármacos
14.
Ann Thorac Surg ; 67(4): 1083-90, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10320255

RESUMO

BACKGROUND: The extent to which the endothelium regulates radial artery (RA) contractions is unknown. The goals of this study were to characterize endothelium-dependent relaxations in the RA, compare these responses with those in the internal mammary artery (IMA), and, subsequently, manipulate nitric oxide production in the RA with adenovirus-mediated gene transfer. METHODS: Segments of RA and IMA from 43 patients were studied initially in organ chambers. Endothelial function was evaluated and gene transfer, was examined. RESULTS: After precontraction to 80% maximum tension with prostaglandin F2alpha, acetylcholine produced lesser relaxations in the RA (21.5%+/-5.8%) than in the IMA (66.7%+/-10.6%); human thrombin and adenosine 5'-diphosphate yielded similar results. Reduced relaxations in the RA (16.8%+/-4.2%) compared with those in the IMA (71.6%+/-11.9%) were noted with calcium ionophore. Superfusion bioassay demonstrated a similar baseline release in both arteries but a reduced stimulated production of vasoactive substances in the RA, results confirmed by cyclic guanosine monophosphate level determination. The RA produced less 6-keto-prostaglandin F1alpha than the IMA. Light microscopy demonstrated an intact endothelium in both arteries. Adenovirus-mediated gene transfer of nitric oxide synthase augmented relaxations of the RA to acetylcholine. CONCLUSIONS: Reduced production of endothelium-derived relaxing factors suggests diminished endothelial regulation of vascular smooth muscle in the RA compared with the IMA. This finding may explain, in part, the predisposition to vasoconstriction in RA grafts.


Assuntos
Endotélio Vascular/fisiologia , Artéria Torácica Interna/fisiologia , Artéria Radial/fisiologia , Vasoconstrição/fisiologia , 6-Cetoprostaglandina F1 alfa/análise , Acetilcolina/farmacologia , Difosfato de Adenosina/farmacologia , GMP Cíclico/análise , Dinoprosta/farmacologia , Técnicas de Transferência de Genes , Humanos , Ionóforos/farmacologia , Artéria Torácica Interna/química , Artéria Torácica Interna/citologia , Músculo Liso Vascular/fisiologia , Óxido Nítrico/biossíntese , Técnicas de Cultura de Órgãos , Artéria Radial/química , Artéria Radial/citologia , Trombina/farmacologia , Vasodilatadores/farmacologia
15.
Curr Opin Cardiol ; 13(6): 447-52, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9822878

RESUMO

In recent years, the use of the radial artery as a coronary artery bypass graft has enjoyed a revival. This follows the initial disappointing results with the use of this blood vessel experienced by Carpentier and colleagues in the early 1970s. The improvement in the performance of the radial artery is believed to be caused by improved harvesting techniques and the use of vasodilator drugs. However, compared with the other blood vessels used as bypass grafts, little is known about the vascular biology of this artery. The reactivity of the smooth muscle and protection offered by the vascular endothelium are known to be important factors that may determine the suitability of different arteries and veins to act as bypass conduits. The aim of this review is to examine how the properties of the vessel wall may contribute to the performance of the radial artery when used as a coronary artery bypass graft.


Assuntos
Artéria Radial , Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Endotélio Vascular/fisiologia , Humanos , Artéria Radial/citologia , Artéria Radial/fisiologia , Artéria Radial/transplante , Vasoconstrição
16.
Ann Thorac Surg ; 66(6): 1972-6; discussion 1976-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9930479

RESUMO

BACKGROUND: Variations in the morphology and vascular reactivity of the proximal and distal radial artery might influence its performance as a bypass conduit. METHODS: The morphologic and functional characteristics of the proximal and distal RAs were compared with those of the left and right internal mammary arteries by using histologic and in vitro organ bath techniques. RESULTS: Proximal RA had a significantly greater medial cross-sectional area compared with that of the distal RA (2.48+/-0.27 mm2 compared with 1.86+/-0.21 mm2, p< 0.05), which were both significantly greater than the left internal mammary artery (0.54+/-0.09 mm2) or the right internal mammary artery (0.67+/-0.03 mm2). Proximal RA had a significantly greater response to 90 mmol/L potassium chloride than that of distal RA (88.4+/-7.3 compared with 60.2+/-10.3 mN, p<0.05), and both contracted more than the left internal mammary artery (30.3+/-2.9 mN) and the right internal mammary artery (32.6+/-4.1 mN). There was no difference in the response to noradrenaline and adrenaline between proximal and distal RA, both of which contracted more than the left and right internal mammary arteries. CONCLUSIONS: When choosing a segment of RA for use as a bypass conduit, regional variations in biologic properties should be considered.


Assuntos
Ponte de Artéria Coronária/métodos , Artéria Radial/citologia , Artéria Radial/fisiologia , Idoso , Feminino , Humanos , Masculino , Artéria Torácica Interna/anatomia & histologia , Artéria Torácica Interna/fisiologia , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Artéria Radial/transplante , Vasoconstrição/fisiologia
17.
Coron Artery Dis ; 8(3-4): 225-33, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9237033

RESUMO

The radial artery is being used with increasing frequency to replace the saphenous vein as a coronary artery bypass graft, on the basis of the belief that it will provide improved long-term patency. Innovative techniques in assessing the ulnar collateral circulation to the hand continue to evolve, giving comfort to the surgeon. Several centres have confirmed that the early results of surgery using the radial artery are similar to those using conventional grafts. Few late graft patency results or clinical data have been reported. Unresolved issues, such as the importance of pathological changes in the radial artery, the prevention of spasm, and the hypoperfusion syndrome, lurk in the background. The role of the radial artery continues to evolve.


Assuntos
Ponte de Artéria Coronária/métodos , Artéria Radial , Ponte de Artéria Coronária/mortalidade , Ponte de Artéria Coronária/normas , Doença das Coronárias/cirurgia , Sobrevivência de Enxerto , Humanos , Artéria Radial/citologia , Artéria Radial/fisiologia , Artéria Radial/cirurgia , Taxa de Sobrevida , Vasoconstrição
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