RESUMEN
Energy drinks are nonalcoholic beverages whose main ingredients are sugar, taurine, and caffeine. The consumption of energy drinks is increasing worldwide, but only a few conflicting studies have investigated the vascular effects of energy drinks in young adults. The aim of this study was to evaluate microvascular reactivity before and after energy drinks consumption in young healthy male volunteers. This was a cross-sectional prospective study. Microvascular reactivity signals were evaluated in the skin of the forearm using laser speckle contrast imaging with acetylcholine (ACh) iontophoresis before and 90 and 180 min after the randomized consumption of one ED or the same volume of water (control), followed by a postocclusive reactive hyperemia (PORH) test. Thirty-two volunteers were evaluated (age: 25.4±4.3 years). Energy drink consumption prevented the rest-induced reduction in cutaneous vascular conductance over time that was observed in the control group. In the control group, there were significant reductions in microvascular vasodilation at 90 and 180 min compared to baseline (P=0.004), but this was not the case in the energy drink group (P=0.76). Our results demonstrated that the reduction in microvascular conductance associated with prolonged immobility can be prevented by the consumption of one energy drink, highlighting the vasodilator effects of this beverage in young individuals at rest. The between-study variability in terms of the brand of energy drinks and the ingested volume, as well as the method of vascular evaluation and the inclusion criteria, may explain the discrepancies among previous studies on the vascular effects of energy drinks.
Asunto(s)
Bebidas Energéticas , Humanos , Masculino , Adulto , Estudios Prospectivos , Estudios Transversales , Adulto Joven , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Descanso/fisiología , Antebrazo/irrigación sanguínea , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Hiperemia , Microvasos/efectos de los fármacos , Acetilcolina/administración & dosificación , Acetilcolina/farmacologíaRESUMEN
Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.
Asunto(s)
Insuficiencia Cardíaca , Vasodilatación , Anciano , Suplementos Dietéticos , Endotelio Vascular , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Masculino , Microcirculación , Persona de Mediana Edad , Proyectos Piloto , Piel , Vasodilatadores/farmacología , Proteína de Suero de Leche/farmacologíaRESUMEN
Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Anciano , Vasodilatación , Insuficiencia Cardíaca/tratamiento farmacológico , Piel , Vasodilatadores/farmacología , Endotelio Vascular , Proyectos Piloto , Suplementos Dietéticos , Proteína de Suero de Leche/farmacología , MicrocirculaciónRESUMEN
The sympathetic nervous system (SNS) plays a fundamental role in the pathophysiology of cardiovascular diseases, including primary arterial hypertension. In this study, we aimed to investigate whether the expression of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and the ß2-adrenergic receptor (ß2-AR) in immune cells from peripheral blood, reflect central SNS activity in spontaneously hypertensive rats (SHR). TH expression in the lower brainstem and adrenal glands and ß2-AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and ß2-AR expression was evaluated by flow cytometry before and after chronic treatment with the centrally-acting sympathoinhibitory drug clonidine. Western blot analyses showed increased TH and ß2-AR expression in the lower brainstem and increased TH in adrenal glands from SHR compared to normotensive Wistar Kyoto rats (WKY). Lower brainstem from SHR treated with clonidine presented reduced TH and ß2-AR levels, and adrenal glands had decreased TH expression compared to SHR treated with vehicle. Flow cytometry showed that the percentage of leukocytes that express ß2-AR is higher in SHR than in WKY. However, the percentage of leukocytes that expressed TH was higher in WKY than in SHR. Moreover, chronic treatment with clonidine normalized the levels of TH and ß2-AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and ß2-AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.
Asunto(s)
Hipertensión , Animales , Presión Sanguínea , Hipertensión/tratamiento farmacológico , Leucocitos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores Adrenérgicos beta 2 , Sistema Nervioso Simpático , Tirosina 3-MonooxigenasaRESUMEN
The sympathetic nervous system (SNS) plays a fundamental role in the pathophysiology of cardiovascular diseases, including primary arterial hypertension. In this study, we aimed to investigate whether the expression of the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and the β2-adrenergic receptor (β2-AR) in immune cells from peripheral blood, reflect central SNS activity in spontaneously hypertensive rats (SHR). TH expression in the lower brainstem and adrenal glands and β2-AR expression in the lower brainstem were analyzed by western blot analyses. In the leukocytes, TH and β2-AR expression was evaluated by flow cytometry before and after chronic treatment with the centrally-acting sympathoinhibitory drug clonidine. Western blot analyses showed increased TH and β2-AR expression in the lower brainstem and increased TH in adrenal glands from SHR compared to normotensive Wistar Kyoto rats (WKY). Lower brainstem from SHR treated with clonidine presented reduced TH and β2-AR levels, and adrenal glands had decreased TH expression compared to SHR treated with vehicle. Flow cytometry showed that the percentage of leukocytes that express β2-AR is higher in SHR than in WKY. However, the percentage of leukocytes that expressed TH was higher in WKY than in SHR. Moreover, chronic treatment with clonidine normalized the levels of TH and β2-AR in leukocytes from SHR to similar levels of those of WKY. Our study demonstrated that the percentage of leukocytes expressing TH and β2-AR was altered in arterial hypertension and can be modulated by central sympathetic inhibition with clonidine treatment.
Asunto(s)
Animales , Ratas , Hipertensión/tratamiento farmacológico , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Sistema Nervioso Simpático , Tirosina 3-Monooxigenasa , Presión Sanguínea , Receptores Adrenérgicos beta 2 , LeucocitosRESUMEN
There is no definite recommendation for testing platelet aggregation (PA) in acute coronary syndromes (ACS) due to inconclusive evidence on the usefulness of platelet function tests to guide therapy and improve clinical outcomes. The evaluation of PA with multiple electrode impedance platelet aggregometry (MEA) may be useful to manage antiplatelet therapy and possibly influence patient outcome. The primary aim of this study was to measure PA with MEA in Brazilian patients with ACS and evaluate the association between PA and adverse clinical outcomes. Forty-seven consecutive patients admitted with ACS to a Brazilian tertiary-care public hospital were studied and PA was evaluated using MEA. Patients were followed for six months for the occurrence of all-cause death, acute myocardial infarction, or stroke. Suboptimal inhibition of PA was found in 7 patients (14.9%); 5 (10.6%) in response to ASA (acetylsalicylic acid), 2 (5.0%) to clopidogrel, and none to ticagrelor. Inadequate PA inhibition in response to ASA was significantly associated with the composite end point, but there was no significant association for insufficient PA inhibition in response to clopidogrel. This study suggested that the evaluation of PA in ACS using MEA may identify non-responders to ASA. Larger studies are necessary to define, in a public health scenario, the value of MEA in the management of ACS.
Asunto(s)
Síndrome Coronario Agudo/sangre , Impedancia Eléctrica/uso terapéutico , Agregación Plaquetaria , Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina/uso terapéutico , Aspirina/uso terapéutico , Femenino , Hospitales Públicos , Humanos , Masculino , Proyectos Piloto , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Estudios Prospectivos , Receptores Purinérgicos P2Y12/sangre , Centros de Atención TerciariaRESUMEN
There is no definite recommendation for testing platelet aggregation (PA) in acute coronary syndromes (ACS) due to inconclusive evidence on the usefulness of platelet function tests to guide therapy and improve clinical outcomes. The evaluation of PA with multiple electrode impedance platelet aggregometry (MEA) may be useful to manage antiplatelet therapy and possibly influence patient outcome. The primary aim of this study was to measure PA with MEA in Brazilian patients with ACS and evaluate the association between PA and adverse clinical outcomes. Forty-seven consecutive patients admitted with ACS to a Brazilian tertiary-care public hospital were studied and PA was evaluated using MEA. Patients were followed for six months for the occurrence of all-cause death, acute myocardial infarction, or stroke. Suboptimal inhibition of PA was found in 7 patients (14.9%); 5 (10.6%) in response to ASA (acetylsalicylic acid), 2 (5.0%) to clopidogrel, and none to ticagrelor. Inadequate PA inhibition in response to ASA was significantly associated with the composite end point, but there was no significant association for insufficient PA inhibition in response to clopidogrel. This study suggested that the evaluation of PA in ACS using MEA may identify non-responders to ASA. Larger studies are necessary to define, in a public health scenario, the value of MEA in the management of ACS.
Asunto(s)
Agregación Plaquetaria/efectos de los fármacos , Impedancia Eléctrica/uso terapéutico , Síndrome Coronario Agudo/sangre , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Inhibidores de Agregación Plaquetaria/uso terapéutico , Adenosina/uso terapéutico , Proyectos Piloto , Aspirina/uso terapéutico , Estudios Prospectivos , Síndrome Coronario Agudo/tratamiento farmacológico , Receptores Purinérgicos P2Y12/sangre , Centros de Atención Terciaria , Hospitales PúblicosRESUMEN
The primary aim of this study was to evaluate penile endothelial microvascular function in patients with primary arterial hypertension and age-matched normotensive subjects using laser speckle contrast imaging (LSCI). Additionally, we analyzed the acute penile microvascular effects induced by oral phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration. Endothelium-dependent microvascular reactivity was evaluated in the penises and forearms of hypertensive patients (aged 58.8±6.6 years, n=34) and age-matched healthy volunteers (n=33) at rest and 60 min following oral SIL (100 mg) administration. LSCI was coupled with cutaneous acetylcholine (ACh) iontophoresis using increasing anodal currents. Basal penile cutaneous vascular conductance (CVC) values were not significantly different between control subjects and hypertensive individuals. Penile CVC values increased significantly after SIL administration in control (P<0.0001) and hypertensive (P<0.0001) subjects. Peak CVC values were not different between the two groups during penile ACh iontophoresis before SIL administration (P=0.2052). Peak CVC values were higher in control subjects than in hypertensive subjects after SIL administration (P=0.0427). Penile endothelium-dependent microvascular function is, to some extent, preserved in patients presenting with primary arterial hypertension under effective anti-hypertensive treatment. LSCI may be a valuable non-invasive tool for the evaluation of penile vascular responses to phosphodiesterase type 5 inhibitor.
Asunto(s)
Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Pene/irrigación sanguínea , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Citrato de Sildenafil/administración & dosificación , Anciano , Estudios de Casos y Controles , Voluntarios Sanos , Humanos , Flujometría por Láser-Doppler/métodos , Masculino , Microcirculación , Persona de Mediana Edad , Pene/efectos de los fármacos , Flujo Sanguíneo Regional , Vasodilatación/efectos de los fármacosRESUMEN
The primary aim of this study was to evaluate penile endothelial microvascular function in patients with primary arterial hypertension and age-matched normotensive subjects using laser speckle contrast imaging (LSCI). Additionally, we analyzed the acute penile microvascular effects induced by oral phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration. Endothelium-dependent microvascular reactivity was evaluated in the penises and forearms of hypertensive patients (aged 58.8±6.6 years, n=34) and age-matched healthy volunteers (n=33) at rest and 60 min following oral SIL (100 mg) administration. LSCI was coupled with cutaneous acetylcholine (ACh) iontophoresis using increasing anodal currents. Basal penile cutaneous vascular conductance (CVC) values were not significantly different between control subjects and hypertensive individuals. Penile CVC values increased significantly after SIL administration in control (P<0.0001) and hypertensive (P<0.0001) subjects. Peak CVC values were not different between the two groups during penile ACh iontophoresis before SIL administration (P=0.2052). Peak CVC values were higher in control subjects than in hypertensive subjects after SIL administration (P=0.0427). Penile endothelium-dependent microvascular function is, to some extent, preserved in patients presenting with primary arterial hypertension under effective anti-hypertensive treatment. LSCI may be a valuable non-invasive tool for the evaluation of penile vascular responses to phosphodiesterase type 5 inhibitor.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Anciano , Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Pene/irrigación sanguínea , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Citrato de Sildenafil/administración & dosificación , Estudios de Casos y Controles , Voluntarios Sanos , Flujometría por Láser-Doppler/métodos , Microcirculación , Pene/efectos de los fármacos , Flujo Sanguíneo Regional , Vasodilatación/efectos de los fármacosRESUMEN
Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.
Asunto(s)
Enfermedad de la Arteria Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Flujometría por Láser-Doppler/métodos , Microvasos/fisiopatología , Imagen de Perfusión/métodos , Anciano , Estudios de Casos y Controles , Medios de Contraste , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Transversales , Endotelio Vascular/diagnóstico por imagen , Humanos , Hiperemia/fisiopatología , Masculino , Microcirculación/fisiología , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Proyectos Piloto , Reproducibilidad de los Resultados , Piel/irrigación sanguínea , Estadísticas no ParamétricasRESUMEN
Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Flujometría por Láser-Doppler/métodos , Microvasos/fisiopatología , Imagen de Perfusión/métodos , Estudios de Casos y Controles , Medios de Contraste , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Transversales , Endotelio Vascular/diagnóstico por imagen , Hiperemia/fisiopatología , Microcirculación/fisiología , Microvasos/diagnóstico por imagen , Proyectos Piloto , Reproducibilidad de los Resultados , Piel/irrigación sanguínea , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) is associated with systemic inflammatory response and endothelial dysfunction. Our hypothesis is that CPB-induced post-operative endothelial dysfunction may be detected using laser Doppler perfusion monitoring (LDPM) in the skin microcirculation. METHODS: We used LDPM to investigate the subacute effects of the CPB on systemic microvascular reactivity among patients undergoing CABG surgery with CPB. Thirty patients were submitted to the study of skin microcirculation and blood sample collection at baseline (pre-surgery) and at 7 days post-surgical procedure. The skin microcirculation was evaluated by acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, and thermal hyperemia (TH). Plasma levels of nitrite/nitrate were also analyzed, and cytokine profiles were determined using a multiplex system. RESULTS: On-pump CABG surgery induced a significant reduction of the increased microvascular dermal flux observed after cumulative doses of ACh iontophoresis and after TH. On-pump CABG surgery did not induce any significant changes in the microvascular flux after cumulative doses of SNP. Patients still presented high levels of interleukin (IL)-6, IL-8, and C-reactive protein, and low bioavailability of nitric oxide 7 days after the CABG surgery with CPB. CONCLUSION: We observed a significant impairment of systemic microvascular endothelial function and well-preserved endothelium-independent vasodilatation in the skin microcirculation of patients 1 week after CABG surgery with CPB. Our results suggest that LDPM is a useful tool for the assessment of on-pump CABG-induced subacute post-operative endothelial dysfunctions.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Endotelio Vascular/fisiopatología , Complicaciones Posoperatorias/fisiopatología , Enfermedades Vasculares/fisiopatología , Acetilcolina , Capilares/efectos de los fármacos , Capilares/fisiología , Puente Cardiopulmonar/efectos adversos , Puente de Arteria Coronaria , Citocinas/sangre , Femenino , Calor , Humanos , Hiperemia/fisiopatología , Cuidados Intraoperatorios , Iontoforesis , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Nitratos/sangre , Óxido Nítrico/sangre , Nitroprusiato , Perfusión , Periodo Posoperatorio , VasodilatadoresRESUMEN
Sepsis is a severe disorder characterized by systemic inflammatory responses in the presence of an infection and may progress to multiple organ dysfunction and death. Alterations in cerebral microcirculation fulfill a crucial role in the pathogenesis of severe sepsis, and include a decrease in capillary density and disturbances in leukocyte movement along capillaries. Nevertheless, the mechanisms involved in sepsis-associated cerebral microcirculatory alterations have so far not been defined. We investigated the effect of the peroxisome proliferator-activated receptor gamma (PPARγ) selective agonist rosiglitazone on leukocyte/endothelial cell interaction and functional capillary density in the brain in the cecal ligation and puncture (CLP) model of sepsis. Anti-inflammatory effects of rosiglitazone on the cerebral microcirculation were marked. Functional capillary density increased and leukocyte rolling and adhesion were decreased in animals submitted to CLP and treated with rosiglitazone. Our data provide evidence for involvement of PPARγ activation in leukocyte-endothelium interactions and alterations in capillary density. Improved cerebral perfusion in animals treated with rosiglitazone, suggests that PPARγ activation is protective against cerebral microvascular dysfunction in sepsis.
Asunto(s)
Antiinflamatorios/farmacología , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/efectos de los fármacos , Trastornos Cerebrovasculares/prevención & control , Microcirculación/efectos de los fármacos , Microvasos/efectos de los fármacos , PPAR gamma/agonistas , Sepsis/tratamiento farmacológico , Tiazolidinedionas/farmacología , Animales , Ciego/cirugía , Trastornos Cerebrovasculares/inmunología , Trastornos Cerebrovasculares/metabolismo , Trastornos Cerebrovasculares/fisiopatología , Citoprotección , Modelos Animales de Enfermedad , Rodamiento de Leucocito/efectos de los fármacos , Ligadura , Masculino , Ratones , Microvasos/inmunología , Microvasos/metabolismo , Microvasos/fisiopatología , Infiltración Neutrófila/efectos de los fármacos , PPAR gamma/metabolismo , Punciones , Rosiglitazona , Sepsis/inmunología , Sepsis/metabolismo , Sepsis/fisiopatologíaRESUMEN
AIMS: Recent data identified uric acid as an independent risk factor for cardiovascular disease. The aim of the present study was to assess the association between uric acid and endothelial dysfunction in 57 patients with Type 1 diabetes and 53 healthy control subjects. METHODS: Microvascular endothelial function was evaluated using laser Doppler perfusion monitoring coupled with pharmacological (iontophoretic administration of acetylcholine and sodium nitroprusside) and physiological (post-occlusive reactive hyperaemia and thermal hyperaemia) stimuli. RESULTS: Uric acid was higher in subjects without diabetes than in those with diabetes (P = 0.03). Microvascular vasodilator response to acetylcholine was significantly reduced in Type 1 diabetes (P = 0.002) and was correlated to disease duration (r = -0.3, P = 0.01), triglyceride (r = -0.37, P = 0.005), insulin dose (r = -0.28, P = 0.03), fasting plasma glucose levels (r = -0.3, P = 0.02), HbA(1c) (r = -0.34, P = 0.001) and uric acid (r = -0.3, P = 0.005). On stepwise multivariate analysis, age, HbA(1c) and uric acid were the most important independent variables that were associated with the endothelium-dependent response in Type 1 diabetes (P = 0.02). CONCLUSIONS: Glycaemic control and uric acid in the normal range were the most important contributing factors to the decreasing endothelium-dependent responses associated with Type 1 diabetes. Consequently, uric acid could be a new potential marker of microvascular endothelial dysfunction in these patients. Further studies are required to explore the clinical relevance of the relationship between uric acid levels, oxidative stress and endothelial dysfunction in patients with Type 1 diabetes, as well as whether treatment with uric acid-lowering drugs for slight elevations in uric acid would benefit these patients.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Angiopatías Diabéticas/metabolismo , Endotelio Vascular/metabolismo , Microcirculación , Ácido Úrico/sangre , Adulto , Análisis de Varianza , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/fisiopatología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Flujometría por Láser-Doppler , Masculino , Microcirculación/efectos de los fármacos , Adulto JovenRESUMEN
OBJECTIVE: We have shown previously that exercise training enhances endothelium-dependent and endothelium-independent vascular relaxation in rabbit kidney. This study aimed to investigate protein expression changes in the rabbit renal cortex induced by chronic dynamic exercise. DESIGN: Kidneys were obtained from New Zealand rabbits either confined to pens (n = 8) or trained on a treadmill (0% grade) for 5 days/week at a speed of 18 m/min for 60-min periods over 12 weeks (n = 8). Expression of proteins in the renal cortex was determined by colloidal Coomassie blue staining after two-dimensional polyacrylamide gel electrophoresis. Differential protein spots were excised and digested with trypsin, and peptides were sequenced by electrospray ionization-ion trap mass spectrometry. RESULTS: Two pairs of matching differentially stained spots displayed an approximate threefold increase in trained compared with sedentary animals. These four spots presented a molecular mass of 23 kDa but different pI values. Mass spectrometric analyses revealed the pairs of matching spots as being rabbit apolipoprotein A-I. CONCLUSION: Chronic dynamic exercise increases apolipoprotein A-I expression in the rabbit renal cortex. This fact could be involved in the alterations observed in the renal circulation after exercise training.
Asunto(s)
Apolipoproteína A-I/metabolismo , Corteza Renal/fisiología , Condicionamiento Físico Animal/fisiología , Animales , Electroforesis en Gel Bidimensional , Proteómica , Conejos , Distribución AleatoriaRESUMEN
The aim of the present study was to evaluate skin capillary density and recruitment of the upper and lower extremities of patients with type 1 diabetes under chronic treatment without clinical manifestations of diabetes-related complications. This cross-sectional observational study included 59 (27.1+/-10.6 years) consecutive outpatients with type 1 diabetes [duration 10 (1; 45) years] and 41 age- and sex-matched healthy controls. We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities as well as capillary recruitment using post-occlusive reactive hyperemia (PORH) in the dorsum of the fingers and toes. Mean capillary density (MCD) of the fingers at baseline was not different between controls and patients (123.02+/-22.6 and 132.3+/-28.9 capillaries/mm(2), respectively; P=0.08). In contrast, baseline MCD of the toes was lower in controls, when compared to patients (84.6+/-19.8 and 96.2+/-23.4 capillaries/mm(2), respectively; P=0.01). Capillary recruitment during PORH (% increase of the number of capillaries/mm(2)) was significantly higher in controls compared to patients both in fingers [7 (-8; 33) and -1.0 (-35, 13), respectively; P=0.000] and toes [6 (-20; 46) and 0 (-24; 20), respectively; P=0.000]. During venous occlusion, capillary density increase (% increase of the number of capillaries/mm(2)) was also higher in controls compared to patients both in fingers [3 (-14; 23) and 0.0 (-30; 29.2), respectively; P=0.02] and toes [9.3 (-18; 51) and -7 (-34; 22), respectively; P=0.000]. Our results showed that patients with type 1 diabetes, although not presenting skin capillary rarefaction, display skin microvascular functional alterations in both extremities characterized by an absence of capillary reserve.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Endotelio Vascular/fisiopatología , Adulto , Capilares/fisiopatología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Dedos/irrigación sanguínea , Humanos , Hiperemia/fisiopatología , Masculino , Microscopía por Video , Piel/irrigación sanguínea , Dedos del Pie/irrigación sanguíneaRESUMEN
High glucose concentrations are involved in the development of diabetic-associated vascular complications. We have previously reported that acute high glucose challenge, corresponding to post-prandial glycemia levels observed in patients with type 2 diabetes, blunts ACh-induced endothelium-dependent relaxation of the renal circulation of non-diabetic rabbits. Isolated perfused kidneys from non-diabetic rabbits were acutely exposed (3 h) to normal (5.5 mM--control group) or high (15 mM) D-glucose concentrations in the presence or absence of a continuous infusion of metformin (20 or 100 microM). Renal vascular reactivity was evaluated with endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) vasodilating agents. ACh-induced maximal renal vasodilation was reduced by high glucose infusion (15 mM) in comparison to the control group (25+/-3% and 41+/-3% respectively; P<0.01), being restored to 41+/-4% and 43+/-2% by a simultaneous 3-h infusion of 20 or 100 microM of metformin respectively (P>0.05). Perfusion of the kidneys with the angiotensin II-converting enzyme inhibitor captopril (10 microM) also significantly prevented the deleterious effects of high glucose challenge in the renal circulation. The use of a continuous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not affect the protective effect of metformin in the renal circulation (39+/-4%; P>0.05), while tetraethylammonium (TEA, 10 mM) partially blunted this effect (33+/-4, P<0.01). Renal vasodilation induced by SNP was not modified by simultaneous infusion of high glucose and/or metformin. It is concluded that the impairment of ACh-induced endothelium-dependent renal vasodilation observed after acute exposure to high glucose concentrations is abolished by metformin administration. These alterations of renal vascular reactivity can be accounted for, at least in part, by the activation of the renal renin-angiotensin system during hyperglycemia. The protective effects of metformin present some EDHF-dependent component and are not related to metabolic pathways dependent on nitric oxide.
Asunto(s)
Endotelio Vascular/efectos de los fármacos , Hipoglucemiantes/farmacología , Riñón/irrigación sanguínea , Metformina/farmacología , Circulación Renal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Acetilcolina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Captopril/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Glucosa/administración & dosificación , Masculino , Perfusión , Conejos , Tetraetilamonio/farmacología , Vasodilatadores/farmacologíaRESUMEN
We investigated the acute effects of centrally acting antihypertensive drugs on the microcirculation of pentobarbital-anesthetized spontaneously hypertensive rats (SHR). The effects of the sympatho-inhibitory agents clonidine and rilmenidine, known to activate both alpha2-adrenoceptors and nonadrenergic I1-imidazoline binding sites (I1BS) in the central nervous system, were compared to those of dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H -pyrrol-2-yl)-amine hydrochloride (LNP 509), which selectively binds to the I1BS. Terminal mesenteric arterioles were observed by intravital microscopy. Activation of the central sympathetic system with L-glutamate (125 µg, ic) induced marked vasoconstriction of the mesenteric microcirculation (27 ± 3 percent; N = 6, P < 0.05). In contrast, the marked hypotensive and bradycardic effects elicited by intracisternal injection of clonidine (1 µg), rilmenidine (7 µg) and LNP 509 (60 µg) were accompanied by significant increases in arteriolar diameter (12 ± 1, 25 ± 10 and 21 ± 4 percent, respectively; N = 6, P < 0.05). The vasodilating effects of rilmenidine and LNP 509 were two-fold higher than those of clonidine, although they induced an identical hypotensive effect. Central sympathetic inhibition elicited by baclofen (1 µg, ic), a GABA B receptor agonist, also resulted in vasodilation of the SHR microvessels. The acute administration of clonidine, rilmenidine and LNP 509 also induced a significant decrease of cardiac output, whereas a decrease in systemic vascular resistance was observed only after rilmenidine and LNP 509. We conclude that the normalization of blood pressure in SHR induced by centrally acting antihypertensive agents is paralleled by important vasodilation of the mesenteric microcirculation. This effect is more pronounced with substances acting preferentially (rilmenidine) or exclusively (LNP 509) upon I1BS than with those presenting important alpha2-adrenergic activity (clonidine).
Asunto(s)
Animales , Ratas , Antihipertensivos , Clonidina , Microcirculación , Circulación Esplácnica , Ratas Endogámicas SHR , Sistema Nervioso Simpático , VasodilataciónRESUMEN
We investigated the acute effects of centrally acting antihypertensive drugs on the microcirculation of pentobarbital-anesthetized spontaneously hypertensive rats (SHR). The effects of the sympatho-inhibitory agents clonidine and rilmenidine, known to activate both alpha2-adrenoceptors and nonadrenergic I1-imidazoline binding sites (I1BS) in the central nervous system, were compared to those of dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2-yl)-amine hydrochloride (LNP 509), which selectively binds to the I1BS. Terminal mesenteric arterioles were observed by intravital microscopy. Activation of the central sympathetic system with L-glutamate (125 microg, ic) induced marked vasoconstriction of the mesenteric microcirculation (27 +/- 3%; N = 6, P < 0.05). In contrast, the marked hypotensive and bradycardic effects elicited by intracisternal injection of clonidine (1 microg), rilmenidine (7 microg) and LNP 509 (60 microg) were accompanied by significant increases in arteriolar diameter (12 +/- 1, 25 +/- 10 and 21 +/- 4%, respectively; N = 6, P < 0.05). The vasodilating effects of rilmenidine and LNP 509 were two-fold higher than those of clonidine, although they induced an identical hypotensive effect. Central sympathetic inhibition elicited by baclofen (1 microg, ic), a GABA B receptor agonist, also resulted in vasodilation of the SHR microvessels. The acute administration of clonidine, rilmenidine and LNP 509 also induced a significant decrease of cardiac output, whereas a decrease in systemic vascular resistance was observed only after rilmenidine and LNP 509. We conclude that the normalization of blood pressure in SHR induced by centrally acting antihypertensive agents is paralleled by important vasodilation of the mesenteric microcirculation. This effect is more pronounced with substances acting preferentially (rilmenidine) or exclusively (LNP 509) upon I1BS than with those presenting important alpha2-adrenergic activity (clonidine).