Hypertension Clinical Trial
Official title:
Effects of Aldosterone Antagonism on Insulin-mediated Microvascular Function in Subjects With the Metabolic Syndrome
The prevalence of obesity and obesity-related complications is currently taking epidemic
proportions. These complications increase the risk of type 2 diabetes and cardiovascular
disease, which are important causes of morbidity and mortality worldwide.
It is important to gain insight in the mechanisms underlying obesity-related complications,
because this may lead to the development of directed therapeutic strategies.
Currently, there is significant evidence that the cause of both insulin resistance and
hypertension must be sought at the level of the microcirculation.
Over activity of the renin-angiotensin-aldosterone system is a potential cause of
microvascular dysfunction. Angiotensin II was indeed found to be implicated in the
pathogenesis of obesity-associated hypertension and insulin resistance, possibly through
interference with the vascular effects of insulin.
Increased aldosterone levels have also been associated with resistant hypertension and
insulin resistance, which is illustrated in patients with primary aldosteronism. Furthermore,
aldosterone is known to exert several detrimental effects on the vasculature, some of which
are offset by mineralocorticoid receptor antagonists.
In obese individuals, plasma aldosterone concentrations are increased as well. We hypothesize
that increased aldosterone levels in adipose persons induce microvascular dysfunction, which
contributes to the development of insulin resistance and hypertension, and mineralocorticoid
receptor antagonism results in improved insulin sensitivity and decreased blood pressure by
counteracting the adverse effects of aldosterone on the microvasculature.
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