Aldosterone, Microvascular Function and Salt-sensitivity
Aldosterone-induced Microvascular Dysfunction as a Cause of Salt-sensitivity in Obesity?
Currently, the incidence of obesity and obesity-related disorders is reaching epidemic proportions, which entails an increasing burden for health care systems. The association of obesity with other risk factors for type 2 diabetes mellitus and cardiovascular disease, such as insulin resistance and hypertension, is often referred to as the metabolic syndrome. During recent years, salt-sensitivity of blood pressure has emerged as an additional cardiovascular risk factor that is related to obesity and other key components of the metabolic syndrome. The underlying pathophysiological mechanisms of these interrelationships are complex and incompletely elucidated. Microvascular dysfunction has been proposed as a link between insulin resistance and hypertension in obese individuals. In addition, impairment of microvascular function was found to be associated with salt-sensitivity of blood pressure. Increased aldosterone levels, as observed in obese individuals, might be a cause of microvascular dysfunction-induced salt-sensitivity and insulin resistance. Aldosterone not only gives rise to sodium-retention in the distal tubule of the kidney, but was also found to impair endothelial function and thus lower NO-availability, which is characteristic of microvascular dysfunction. In addition, elevated aldosterone levels are associated with both hypertension and insulin resistance, which is illustrated in patients with primary aldosteronism, but also in the general population.
The investigators hypothesize that increased aldosterone levels in obese individuals lead to impairment of microvascular function through reduction of NO-availability. This microvascular dysfunction is suggested to play a central role in the pathogenesis of salt-sensitive hypertension and insulin resistance.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Limburg
-
Maastricht, Limburg, Países Bajos, 6229 ER
- Maastricht University
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Obese individuals
- Age 18-65 years
- Caucasian
- Waist circumference > 102 cm (men)/> 88 cm (women)
Lean individuals
- Age 18-65 years
- Caucasian
- Waist circumference < 94 cm (men)/< 80 cm (women)
Exclusion Criteria:
Obese/lean individuals
- Cardiovascular disease (stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death)
- Diabetes mellitus/impaired glucose metabolism (fasting glucose values > 5.6 mmol/L
- Stage 3 hypertension (blood pressure > 180/110 mm Hg)
- Unstable or severe pulmonary disease
- Unstable or severe thyroid disorders
- Inflammatory diseases
- Smoking
- Alcohol use > 2 U/day (women)/> 3 U/day (men)
- Use of antihypertensive, lipid-lowering or glucose-lowering medications
- Use of corticosteroids and regular use of NSAIDs
- eGFR< 60 mL/min
- Impairment of hepatic function
- Pregnancy or lactation
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Comparador activo: Start with low-sodium diet
One week of low-sodium diet, followed by a two-week wash-out period and subsequently, another week of high-sodium diet
|
50 mmol NaCl per 24h
250 mmol NaCl per 24h
|
|
Comparador activo: Start with high-sodium diet
One week of high-sodium diet, followed by a two-week wash-out period and subsequently, another week of low-sodium diet
|
50 mmol NaCl per 24h
250 mmol NaCl per 24h
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Difference in capillary recruitment between low- and high sodium diets
Periodo de tiempo: One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized
|
One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: C.D.A. Stehouwer, MD, PhD, Maastricht University Medical Center
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 47438/IMP10124
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .