Haemodynamical variables versus endothelial hormones in hypertensive and type 2 diabetic patients with endothelial dysfunction.

Leptin is a 167 aminoacid peptidic hormone secreted by adipose tissue. It works mainly in the hypothalamus at thirst signal, but given its closed connections with inflammatory and endothelial systems, also has been postulated that it may exert a regulatory control over blood pressure (BP), interacting with nitric oxide (NO) and C reactive protein (CRP). The cold pressor test (CPT) is a simple test that indirectly determines endothelial dysfunction. In this work, biochemical indicators (CRP, leptin, and NO) and hemodynamic indicators (systolic and diastolic BP) were performed and evaluated in hypertensive, type 2 diabetic, and control subjects during a single CPT for assessment of endothelial dysfunction. A total of 43 subjects, males and females aged 25 to 60 years and divided in three groups, 15 healthy volunteers, 13 hypertensive patients, and 15 patients with type 2 diabetes, were included in the study. A complete clinical history was obtained from each subject, and a complete physical examination, including an electrocardiogram was carried out. During the assay of 30 minutes, 0.9% saline was infused intravenously. CPT was performed to assess the cardiovascular reactivity at minute 15. The cardiovascular variables (systolic and diastolic BP) were measured in minute 0, 16, and 30. In addition, serum variables were obtained at the beginning and at the end of the experiment, and statistical analysis was performed. CPT caused in all subjects a significant increase of BP and pulse. There were no significant differences to CPR and leptin in any group, although we observed significant differences for NO (P < 0.05). Sensitivity and specificity for all biochemical variables resulted in nonsignificant statistical or clinical importance as markers of endothelial dysfunction; however, a positive association was found when leptin and NO were evaluated together (sensitivity: 0.2; specificity. 0.8). CRP, leptin, and NO did not shown any direct and significant association with the hemodynamic variables in this study, although a relationship was noted between NO according to group and biochemical variables when studied altogether.

Effects of metoclopramide and metoclopramide/dopamine on blood pressure and insulin release in normotensive, hypertensive, and type 2 diabetic subjects.

The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. We evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 microg kg min through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, we added an intravenous infusion of DA at 1-3 microg kg min during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus. We conclude that there is a pharmacologic interaction between MTC and DA, that the pressor effects of DA are due to activation to beta and alpha adrenergic receptors, and that the cardiovascular effects of DA in type 2 diabetic subjects are attenuated by a probable defect in sympathetic system and to endothelial dysfunction.

Metabolic and hemodynamic markers of endothelial dysfunction in patients with hypertension and patients with type 2 diabetes during the cold pressor test.

Leptin, a 167-amino acid peptidic hormone secreted by adipose tissue, acts mainly in the arcuate hypothalamus nucleus as a satiety signal, but given its closed connections with inflammatory and endothelial systems, a probable regulatory role in blood pressure (BP) control by interaction with nitric oxide (NO) and C-reactive protein (CRP) has also been described. The cold pressor test (CPT) is a simple test that indirectly determines endothelial dysfunction. In this work, biochemical indicators (CRP, leptin, and NO) and hemodynamic indicators (systolic and diastolic BP) were performed and evaluated in patients with hypertension, patients with type 2, and control subjects during a single CPT for assessment of endothelial dysfunction. A total of 43 subjects aged 25 to 60 years were divided into three groups: 15 healthy volunteers, 13 patients with hypertension, and 15 patients with type 2 diabetes were included in the study. A complete clinical history was obtained from each subject and a complete physical examination, including an electrocardiogram, was carried out. During the 30-minute assay, 0.9% saline solution was infused intravenously. CPT was performed to assess the cardiovascular reactivity at 15 minutes. The cardiovascular variables (systolic and diastolic BP) were measured at 0, 16, and 30 minutes. In addition, serum variables were extracted at the beginning and at the end of the experiment and statistical analysis was performed. CPT caused in all subjects a significant increase in BP and pulse. There were no significant differences in CRP or leptin in all groups, although we observed significant differences for NO (P < 0.05). Sensibility and specificity for all biochemical variables resulted in nonsignificant statistical or clinical importance as markers of endothelial dysfunction; however, a positive association was found when leptin and NO were evaluated together (sensibility, 0.2; specificity, 0.8). CRP, leptin, and NO did not show any direct or significant association with the hemodynamic variables in this study, although a relationship was observed in NO according to group and among biochemical variables when studied together.

Variables hemodinamicas versus hormonas endoteliales en hipertensos y diabéticos tipo 2 con disfunción endotelial / Endothelial hormones versus hemodynamic variables in hypertensive and type 2 diabetics with endothelial dysfunction

La leptina es una hormona peptídica de 167 aminoácidos secretada por el tejido adiposo. Funciona principalmente como una señal de saciedad, actuando en el hipotálamo, pero dadas sus estrechas conexiones con el sistema inflamatorio y endotelial, se ha planteado que además ejerce una acción reguladora sobre la presión arterial, interactuando con el ON (óxido nítrico) y la PCR (proteína C reactiva). La PPF (prueba presora por frío) es una prueba simple que determina en forma indirecta disfunción endotelial. En este trabajo se evaluaron indicadores bioquímicos (PCR, leptina y ON) e indicadores hemodinámicos (PAS y PAD: presión arterial sistólica y diastólica) durante la realización de una PPF en sujetos hipertensos y diabéticos tipo 2 para determinar la presencia de disfunción endotelial. Se incluyeron 43 sujetos, hombres y mujeres, de edades entre 25-60 años divididos en 3 grupos: 15 voluntarios sanos, 13 pacientes con hipertensión, y 15 pacientes con diabetes tipo 2. Una historia médica integral fue obtenida para cada sujeto, incluyendo reposo. Durante el experimento, de 30 minutos de duración, se administró solución salina 0,9%. La PPF, se realizó para medir la reactividad cardiaca al minuto 15. Las variables cardiovasculares (FC, PAS y PAD), fueron medidas en el minuto 0, 16 y 30. Muestras séricas se extrajeron al comienzo y al final del experimento, y tras determinar las variables bioquímicas, se realizó el análisis estadístico. La PPF provocó un aumento significativo de la PA y el pulso en todos los grupos. No se apreciaron diferencias significativas para la PCR y la leptina en todos los grupos, pero sí se apreciaron diferencias manifiestas entre grupos para el óxido nítrico (p < 0,05). Los cálculos de sensibilidad y especificidad para las variables bioquímicas individuales no resultaron de significancia estadística o clínica como marcadores de disfunción entotelial, pero sí se halló asociación entre la leptina junto a oxido nítrico (sensibilidad: 20%).

Relación entre dopamina e insulina en sujetos sanos y diabeticos tipo 2 / Relationship between dopamine and insulin in healthy subjects and type 2 diabetes

Los agonistas de la dopamina ejercen un papel importante en la regulación de los sistemas nervioso central, cardiovascular, renal y endocrino, por la estimulación de los receptores a y ß adrenérgicos y dopaminérgicos específicos DA1 y DA2. Diversos estudios demuestran que los agonistas dopaminérgicos mejoran la hiperglicemia y la hiperlipidemia en ratones obesos y diabéticos. Establecer la relación entre la activación de receptores dopaminérgicos y la secreción de insulina mediante el uso de Metoclopramida (MTC) y dopamina (DA) y determinar mediante variables hemodinámicas la respuesta a la activación de receptores dopaminergicos cardiovasculares en sujetos sanos y diabéticos tipo 2. Se seleccionaron 15 sujetos sanos (controles) y 15 diabéticos tipo 2, entre 29 y 53 años de edad, del sexo masculino y femenino. Se diseño un estudio experimental comparativo de 90 minutos es decir, se administraron infusiones intravenosas de dopamina a 0.5-3 µg/Kg y de MTC (DA2), a 7.5 µg/Kg/min. Se empleó como placebo solución fisiológica. Los parámetros estudiados, a 0', 30', 60' y 90 minutos, incluyeron: insulina, glicemia, hemoglobina glicosilada A1c, HOMA-IR, EKG de 12 derivaciones y medición de FC, PAS, PAD y PAM. Resultados: La dopamina (DA) produjo un incremento en la insulina plasmática, PAS y la frecuencia cardiaca en sujetos sanos, pero no en sujetos diabéticos tipo 2. La MTC indujo un efecto hipotensor en sujetos sanos. MTC y DA, no producen modificaciones significativas en el perfil lipidico de sujetos sanos y diabéticos. Las drogas dopaminèrgicas (MTC y DA) median vía activación de receptores dopaminèrgicos pancreáticos un incremento en la insulina plasmática, y al actuar sobre receptores dopaminèrgicos cardiovasculares modifican las variables hemodinámicas, modificación que es atenuada en pacientes diabéticos probablemente por disfunción endotelial y disautonomìa simpática.

Dopamina ¿modulador de la respuesta cardiovascular en sujetos hipertensos? / Dopamine modulator of the cardiovascular answer in hypertensive subject?

En el presente trabajo se estudió 30 sujetos divididos en grupos de a 10, 10 sanos, 10 hipertensos y 10 diabeticos tipo II. El análisis de los resultados en los sujetos diabeticos revela que la metoclopramida, bloqueante dopaminérgico DA2, reduce la presión arterial sin alterar significativamente la frecuencia del pulso; cuando se añadió dopamina (1 mcg/kg/min) la presión arterial sistólica no se modificó significativamente pero el pulso cardiaco aumentó aunque en menor grado que en los sanos y en los hipertensos. Presumimos que esta respuesta menor en los diabeticos podría estar en relación al cuadro de disautonomía que se observa en los pacientes diabeticos

Receptores de glutamato: implicaciones terapéuticas / Glutamate receptors: therapeutic implications

El glutamato, uno de los neurotransmisores más abundantes en el sistema nervioso, realiza su acción excitadora actuando sobre receptores específicos localizados en la membrana neuronal. Los receptores de glutamato se han clasificado en dos grupos principales: receptores ionotrópicos y metabotrópicos. El receptor NMDA es una proteína muy compleja y tremendamente regulada. Su conductancia al Ca²+ es notablemente alta y es quizá su característica más destacadable y la responsable de muchas de sus funciones. Distintas combinaciones de la subunidad fundamental NR1 con las otras subunidades dan lugar a receptores NMDA con propiedades funcionales diferentes, que pueden estar distribuidas en áreas encefálicas específicas y/o que pueden definir respuestas fisiológicas o patológicas distintas en respuesta al glutamato. Se han localizado receptores de glutamato en SNC, pancreas, hipófisis, glandulas adrenales y gónadas. Particularmente en páncreas, se demostró que GluR1 y GluR4 se hallan limitadas a células secretoras de insulina en la masa central de los islotes pancreáticos. Se conoce que hay receptores de NMDA en osteoblastos, postulándose que puedan participar en el desarrollo de enfermedades como la osteoporosis. En vista de la amplia participación del glutamato en la neurotransmisión así como en el desarrollo de varias patologías, se han intentado ensayos clínicos con varias drogas bloqueantes de los receptores NMDA, principalmente antagonistas ionotrópicos, con resultados prometedores en cuanto a dolor, depresión y Parkinson

Helicobacter pylori: enteropatógeno frecuente del ser humano / Helicobacter pylori: the human being's frequent enteropathogeno

En este artículo se revisan los conceptos recientes en relación a una infección bacteriana cuyo agente causal es Helicobacter Pylori, frecuentemente implicado en cuadros gastrointestinales diversos y responsables directo de la enfermedad úlcero-péptica que además es reconocido como agente carcinógenico tipo I por su asociación con cáncer gastrico. Helicobacter Pylori es un bacilo gram negativo que coloniza la mucosa gástrica de amplia distribución mundial, presentes con una alta frecuencia en pacientes que consultan con sintomatología gastrointestinal, por lo que se analizan aspectos básicos de su fisiología, sus diferentes morfologías que directamente van a repercutir en su patogenicidad y se detallan los mecanismos fisiopatológicos responsables de los diferentes cuadros clínicos, los métodos endoscopicos y de laboratorio específicos para el diagnóstico y los avances más recientes en el tratamiento y profilaxis de la enfermedad

Endothelium and hypertensive disorders in pregnancy.

Pregnancy-induced hypertension is one of the complications that obstetricians fear most due to its sudden appearance, its changing clinical presentation, its rapid evolution, and its association with high fetal and maternal morbidity and mortality. Because of these reasons, preeclampsia has been studied widely. But although the search for answers to many questions about its etiopathogenesis and physiopathology has led to numerous researches, after many years of studies and efforts there still exist obscure and enigmatic aspects about them. Today, various risk factors for the development of this entity have been identified, and a combination of different hypotheses has been proposed to try to find an approximation to the real solution for this problem, which could probably lead to better therapeutic management.

Dopaminergic receptors: a new antihypertensive mechanism.

The neutrotransmitter dopamine, precursor of noradrenaline, induces a variety of cardiovascular and renal physiological responses, including an increase in myocardial contractility and cardiac output without changes in heart rate, passive and active vasodilatation, diuresis and natriuresis. These responses result from its interaction with the dopamine receptors D1, D2, D3, D4 and D5. In addition, recent findings suggest the existence of D6 and D7 receptors. In some types of hypertension dopamine is known to influence the control of arterial pressure by influencing the central and peripheral nervous system and target organs such as the kidneys and adrenal glands. Since dopamine and its derivatives have been shown to have antihypertensive effects, it is important to review the physiological and pharmacological aspects of dopamine and its receptors, and the clinical uses that they could have in the therapy of arterial hypertension.