Hypertension Clinical Trial
Official title:
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.
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