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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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Limburg
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Maastricht, Limburg, Pays-Bas, 6229 ER
- Maastricht University
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Autre
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur actif: 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
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50 mmol NaCl per 24h
250 mmol NaCl per 24h
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Comparateur actif: 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
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50 mmol NaCl per 24h
250 mmol NaCl per 24h
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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Difference in capillary recruitment between low- and high sodium diets
Délai: One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized
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One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: C.D.A. Stehouwer, MD, PhD, Maastricht University Medical Center
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 47438/IMP10124
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