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OBJECTIVE: To assess the association between epicardial adipose tissue thickness (EAT) and plasma adrenomedullin plasma levels in patients with metabolic syndrome (MS). METHODS: Twenty-one patients (12 females and 9 males) with MS according to the International Diabetes Federation guidelines, aged 22-58 years, were enrolled into the study and compared to 19 age-matched control subjects without MS. Plasma glucose, lipid, and adrenomedullin levels were assessed. EAT, left ventricular mass, and carotid intima-media thickness were evaluated by transthoracic two-dimensional echocardiography. RESULTS: No statistically significant differences were found between the groups in age, sex, and height. Body weight, abdominal circumference (AC), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly higher (p=0.0001) in MS patients; this group also showed significantly higher glucose (p=0.001), total cholesterol (p=0.01), LDL-C (p=0.03), VLDL-C (p=0.005), triglyceride (p=0.002), Tg/HDL ratio (p=0.0001), and plasma adrenomedullin (3.49±1.21 vs 1.69±0.92 ng/mL; p=0.0001) levels and lower HDL-C (p=0.02) levels as compared to the control group. EAT was significantly thicker in MS patients compared to the control group (8.45±3.14 vs 5.43±0.96; p=0.0001), showed a positive correlation to BMI (r=0.347; p=0.02), AC (r=0.350; p=0.02), DBP (r=0.346; p=0.02), and adrenomedullin levels (r=0.741; p=0.0001). In multiple linear regression analysis, adrenomedullin was the only parameter associated to EAT (R(2)=0.550; p=0.0001). CONCLUSION: In this small patient group, a statistically significant association was found between EAT and plasma adrenomedullin levels, which may be considered as a potential biomarker of MS.
Assuntos
Tecido Adiposo/patologia , Adrenomedulina/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pericárdio/patologia , Adipócitos/metabolismo , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Adrenomedulina/biossíntese , Adulto , Antropometria , Aterosclerose/patologia , Biomarcadores , Glicemia/análise , Artérias Carótidas/diagnóstico por imagem , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Pericárdio/metabolismo , Células Estromais/metabolismo , Ultrassonografia , Adulto JovemRESUMO
La adrenomedulina es un péptido vasodilatador, presente en el sistema cardiovascular, riñón, pulmón, glándula adrenal y en el adipocito. Este péptido ha venido adquiriendo una importancia creciente en los últimos años, ya que se han descrito niveles elevados del mismo en patologías como el síndrome metabólico, diabetes mellitus tipo 2, hipertensión arterial y en aterosclerosis, lo cual pone de manifiesto su relevancia en la fisiopatología de estos trastornos y su posible uso como marcador de riesgo cardiometabólico. A nivel cardíaco, el efecto inotrópico positivo de este péptido parece estar mediado por un aumento del calcio citosólico, independiente de AMP cíclico; reduce la hipertrofia de los miocardiocitos y en la insuficiencia cardíaca los niveles plasmáticos de adrenomedulina están incrementados. La adrenomedulina tiene efecto vasodilatador sistémico y pulmonar y se encuentra incrementada en el plasma de sujetos con hipertensión arterial esencial y en hipertensos con hiperaldosteronismo primario. En riñón, la adrenomedulina induce efecto diurético y natriurético, aumento de la filtración glomerular y disminución de la reabsorción tubular distal de sodio; sus niveles están elevados en la insuficiencia renal crónica. La adrenomedulina está elevada en pacientes diabéticos con mal control metabólico, pero su papel patogénico en la enfermedad no está claro.
Adrenomedullin is a vasodilatory peptide found in the cardiovascular system, kidneys, lungs, adrenal glands and adipocytes. This peptide has been rising interest during the last years because increased plasma levels of it have been found in several pathological conditions such as the metabolic syndrome, type 2 diabetes mellitus, arterial hypertension and atherosclerosis, pointing to a possible physiopathologic role in these diseases and the potential use as a clinical cardiometabolic marker. In the heart, adrenomedullin has a positive inotropic action, probably mediated through cytosolic increase of calcium concentration, independent of cyclic AMP; it also can reduce cardiomyocites hypertrophy. In heart failure, adrenomedullin levels are increased and show systemic and pulmonar vasodilator effect; its plasma levels are increased in patients with essential arterial hypertension and hypertensives with primary hyperaldosteronism. In the kidneys, adrenomedullin is natriuretic and diuretic, it elevates glomerular filtration rate and reduce distal tubules sodium reabsorption; in patients with renal failure, adrenomedullin levels are increased. In diabetic patients, adrenomedullin plasma levels are increased; however, its pathogenic role in this disease is not yet clear.
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La disfunción endotelial (DE) se presenta en pacientes con hipercolesterolemia, hipertensión arterial, obesidad y diabetes mellitus. Evidencias sugieren un papel de los glicosaminoglicanos en la DE. Evaluamos el efecto del sulodexide (SLD), un glicosaminoglicano utilizado en el tratamiento de la albuminuria y la enfermedad isquémica en pacientes diabéticos, sobre la relajación arterial y los cambios morfológicos en un modelo experimental de diabetes tipo 1. La diabetes se indujo a ratas Sprague Dawley administrando estreptozotocina (STZ), 60 mg/kg, i.v. Los animales fueron distribuidos en los siguientes grupos: I= control, II= diabéticas, III: control + sulodexide, IV= diabéticas + sulodexide (15 mg/kg/día s.c). A los 3 meses fueron sacrificados, las aortas extraídas para evaluar la relajación vascular inducida por acetilcolina (Ach) y nitroprusiato de sodio en anillos precontraídos con fenilefrina. Fueron evaluadas histológicamente mediante microscopía de luz y coloraciones diversas. El SLD in vitro no modificó la tensión basal de los anillos arteriales en reposo o precontraídos con fenilefrina. La diabetes disminuyó la capacidad de relajación arterial en respuesta a la Ach en un 28,8-35,1% vs control, efecto que fue prevenido por SLD. No se observó diferencia significativa en la relajación inducida por nitroprusiato sódico entre los grupos. El estudio histológico en los animales diabéticos mostró alteraciones estructurales, particularmente en la íntima y la adventicia, cambios que fueron prevenidos por el tratamiento con SLD. Nuestros resultados apoyan la potencial utilidad terapéutica del SLD en el tratamiento de la disfunción endotelial.
Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans(GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, iv. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.
Assuntos
Animais , Masculino , Ratos , Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Glicosaminoglicanos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Aorta/patologia , Aorta/fisiopatologia , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Doenças da Aorta/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Endotélio Vascular/ultraestrutura , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacologia , Hipoglicemiantes/farmacologia , Nitroprussiato/farmacologia , Ratos Sprague-Dawley , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/ultraestruturaRESUMO
Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans (GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, i.v. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.
Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Glicosaminoglicanos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Aorta/patologia , Aorta/fisiopatologia , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Doenças da Aorta/fisiopatologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Endotélio Vascular/ultraestrutura , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacologia , Hipoglicemiantes/farmacologia , Masculino , Nitroprussiato/farmacologia , Ratos , Ratos Sprague-Dawley , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/ultraestruturaRESUMO
El síndrome metabólico tiene una fuerte asociación con la patogénesis de la diabetes tipo 2, la hipertensión arterial y las enfermedades cardiovasculares. Los niveles plasmáticos de adiponectina estás disminuidos en los pacientes con síndrome metabólico y diversos estudios demuestran que esta hormona ejerce efectos favorables sobre la aterogénesis, la función endotelial y el remodelado vascular. Esta revisión abordará los estudios tanto epidemiológicos como experimentales que sustentan los efectos pleiotrópicos de la adiponectina en el sistema cardiovascular.
The metabolic syndrome has a strong association with the pathogenesis of type 2 diabetes, arterial hypertension and other cardiovascular diseases. Adiponectin plasma levels are reduced in patients suffering the metabolic syndrome and in many basic and clinical studies have demonstrated that adiponectin improves endothelial function, vascular remodelling and atherogenesis. This review will consider the epidemiological and experimental findings bringing support to the pleiotropic effects adiponectin on the cardiovascular system.
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INTRODUCTION AND OBJECTIVES: To investigate the hemodynamic sympathetic response evoked by NaCI microinjection into the third ventricle anteroventral brain area (AV3V) in rats long-term fed with high fructose diet. METHODS: Twelve male rats received 60% fructose enriched diet for 6 months. Control rats (n=12) received regular diet. RESULTS: Fructose diet increased (P< .01) body weight; plasma glucose, triglycerides; cholesterol, insulin; systolic (SBP) and diastolic blood pressure (DBP). Basal heart rate (HR) did not change. AV3V microinjection of 2 microL of hypertonic 1.5 M NaCI in fructose fed rats increased SBP 44.64(3.6) mm Hg, DBP 19.9(2.4) mm Hg and HR 66.2(8.4) beats/min over basal values (P< .01). In control rats, smaller responses were observed, SBP increased 28.33(3.10) mm Hg, DBP 13.0(1.9) mm Hg and HR 23.0(5.0) beats/min over basal values (P< .01). CONCLUSIONS: Long-term fructose diet in rats induces cardiovascular hyperactivity of AV3V neurons to sodium chloride, and is associated to hypertension and insulin-resistance.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Hipertensão/fisiopatologia , Cloreto de Sódio/administração & dosagem , Animais , Frutose/administração & dosagem , Ventrículos do Coração , Hipertensão/induzido quimicamente , Soluções Hipertônicas , Injeções , Resistência à Insulina , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The crustacean nervous system is an important source of substances with diverse biological activities, particularly affecting invertebrate cardiocirculatory physiology. However, the effects of these substances on the cardiovascular system of higher vertebrates are not very well documented. The purpose of this study was to evaluate the effects of a cardioexcitatory substance (CES) isolated from the eyestalk of the shrimp Peneaus vanameii on rat cardiovascular function. The administration of a purified fraction of this substance raised mean arterial pressure by 37.33 +/- 5.00 mm Hg, pulse pressure 35.00 +/- 4.93 mm Hg and heart rate 80.00 +/- 12.83 beats/min over basal values (p < 0.01). Evaluation of the possible underlying mechanisms of this hypertensive and tachycardic effect reveled that dihydroergotamine pretreatment (20 microg/0.2 mL) reduced the effect of CES on mean blood pressure, but not on heart rate. Propranolol pretreatment (4 microg/0.2 mL) reduced the tachycardia, but not the hypertensive response. Enalapril pretreatment (5 microg/0.2 mL) did not modify the effects induced by CES on heart rate or blood pressure, and the verapamil pretreatment (1 microg/0.2 mL) reduced both cardiovascular changes by 85% (p < 0.01). These results indicate that CES isolated from the shrimp eyestalk produces hypertension and tachycardia mediated by adrenergic receptors in association to calcium channels activation.
Assuntos
Cardiotônicos/farmacologia , Hemodinâmica/efeitos dos fármacos , Neuropeptídeos/farmacologia , Penaeidae/química , Extratos de Tecidos/farmacologia , Estruturas Animais/química , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Canais de Cálcio/efeitos dos fármacos , Cardiotônicos/isolamento & purificação , Di-Hidroergotamina/farmacologia , Di-Hidroergotamina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Enalapril/farmacologia , Enalapril/uso terapêutico , Gânglios dos Invertebrados/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Masculino , Neurônios Motores/efeitos dos fármacos , Neuropeptídeos/isolamento & purificação , Pré-Medicação , Propranolol/farmacologia , Propranolol/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos beta/efeitos dos fármacos , Taquicardia/induzido quimicamente , Taquicardia/prevenção & controle , Extratos de Tecidos/isolamento & purificação , Verapamil/farmacologia , Verapamil/uso terapêuticoRESUMO
El sistema nervioso de crustáceos es una fuente importante de sustancias con actividad biológica diversa, particularmente la que afecta la fisiología cardiocirculatoria de los invertebrados. Sin embargo, los efectos de estas sustancias sobre el sistema cardiovascular de mamíferos no están bien documentados. El objetivo de este estudio, fue evaluar los efectos de una sustancia cardioexcitatoria (SCE) aislada del tallo óptico del camarón Peneaus vanameii sobre la función cardiovascular de la rata. La administración de una fracción purificada de esta sustancia incrementó la presión arterial media en 37,33 ± 5,0 mm de Hg, la presión arterial diferencial en 35,00 ± 4,93 mm de Hg, así como la frecuencia cardiaca 80,00 ± 12,83 lat/min sobre los valores basales (p < 0,01). La evaluación del mecanismo por el cual este efecto hipertensor y taquicardizante se produjo indicó que el tratamiento con dihidroergotamina (20 µg/0,2 mL) redujo los efectos del SCE sobre la presión arterial media, pero no sobre la frecuencia cardiaca. El pretratamiento con propranolol (4 µg/0,2 mL) redujo la taquicardia pero no la respuesta hipertensiva. El pretratamiento con enalapril (5 µg/0,2 mL) no modificó los efectos inducidos por SCE sobre el corazón o los vasos sanguíneos, el pretratamiento con verapamil (1 µg/0,2 mL) redujo ambos cambios cardiovasculares en un 85 por ciento (p < 0,01). Estos resultados indican que el SCE aislado del tallo óptico del camarón produce hipertensión y taquicardia mediada a través de receptores adrenérgicos, en asociación con una activación de los canales de calcio
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Animais , Artemia , Pressão Sanguínea , Sistema Cardiovascular , Biologia , VenezuelaRESUMO
Androgenic steroids increase atherogenesis, thrombogenicity and endothelial dysfunction when administered in high doses, however their effects on NaCl sensitivity of the brain anteroventral area of the third ventricle (DeltaV3V) have not been explored. Sprague-Dawley male rats were anesthetized with sodium pentobarbital (40 mg/kg) and the femoral intra-arterial blood pressure and heart rate monitored through a strain-gauge blood pressure transducer and tachograph. DeltaV3V microinjections of (2 microl) 1.5 mol/l NaCl solution were done according to brain coordinates: AP = 7.0 mm, L = 1.0 mm, D = 7.5 mm through a 0.2-mm diameter stainless steel needle. The injection site was verified with 1.0 microl neutral red solution. Basal systolic blood pressure increased 37.6 and 39.6 mm Hg after testosterone (1 mg/kg/day for 20 days) and nandrolone (1 mg/kg/day for 20 days) treatment respectively; diastolic blood pressure also increased upon testosterone and nandrolone treatment in 36.4 and 53.1 mm Hg, respectively; basal heart rate did not change. Vasopressor response to 1.5 mol/l NaCl DeltaV3V microinjection was higher in testosterone-treated rats; systolic blood pressure increased 56.0 vs. 28.3 control mm Hg; diastolic blood pressure increased 54.0 vs. 25 control mm Hg. This hypertensive response was 29% longer lasting in testosterone compared to vehicle-treated rats. The same pattern of DeltaV3V sensitization to hypertonic NaCl was observed in nandrolone-treated rats. Blood lipid profile changed to a proatherogenic fashion upon testosterone and nandrolone long-term treatment; the plasma-free testosterone concentration increased from 4.9 +/- 0.9 to 36.0 +/-7.1 pg/ml with the same testosterone treatment schedule. In conclusion, long-term androgenic steroid treatment sensitizes the brain DeltaV3V region to hypertonic NaCl which in turn conducts into a sympathetic vasopressor and heart rate-stimulating action.
Assuntos
Androgênios/farmacologia , Encéfalo/efeitos dos fármacos , Hipertensão/fisiopatologia , Nandrolona/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Testosterona/farmacologia , Androgênios/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Sinergismo Farmacológico , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Injeções Intraventriculares , Masculino , Nandrolona/administração & dosagem , Ratos , Ratos Sprague-Dawley , Solução Salina Hipertônica , Testosterona/administração & dosagem , Terceiro Ventrículo/efeitos dos fármacos , Fatores de Tempo , Triglicerídeos/sangueRESUMO
LDL interaction with arterial proteoglycans and its oxidative modification is closely related to atherosclerosis. The objective of the present study was to examine the effect of the individual administration of vitamin E and a combination of vitamin E and C on LDL affinity for arterial proteoglycans in smokers and non-smokers subjects. Twenty smokers and ten non-smokers healthy subjects received by the oral route placebos of vitamins E and C for 15 days; then vitamin E (400 mg/d) for 30 days and finally vitamin E plus vitamin C (1000 mg/d) during the following 30 days. During the vitamin E supplementation period, the affinity of LDL for arterial proteoglycans decreased 19.3% in smokers and 25.2% in non-smokers. When the subjects received vitamin E plus vitamin C, the affinity of LDL for arterial proteoglycans decreased 25.6% and 30.1% in smokers and non-smokers respectively. In conclusion, simultaneous administration of vitamins E and C showed a synergistic effect to diminish the affinity of the LDL by arterial proteoglycans, that was greater than caused by the administration of vitamin E alone. These finding suggest a potential antiatherogenic effect of both antioxidant vitamins.