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Obesity and vitamin D deficiency have both been linked to augmented activity of the tissue renin-angiotensin system (RAS). We investigated whether obesity status influenced the relationship between 25-hydroxyvitamin D (25(OH)D) and vascular RAS activity. The levels of 25(OH)D were measured in hypertensive obese (n=39) and non-obese (n=58) Caucasian individuals. RAS activity was assessed by plasma renin activity, and evaluation of the vascular sensitivity to angiotensin II (AngII) using the mean arterial pressure (MAP) response to an infusion of AngII. Among obese subjects, 25(OH)D was an independent positive predictor of the MAP response to AngII (β=0.70, r=0.41, P<0.01); lower 25(OH)D concentrations were associated with a blunted MAP response to AngII. In contrast, 25(OH)D did not significantly predict the vascular sensitivity to AngII in non-obese subjects (β=0.10, r=0.07, P=0.62). A multivariable-adjusted interaction model confirmed that the positive relationship between 25(OH)D and the vascular sensitivity to AngII strengthened with obesity (P-interaction=0.03). These findings demonstrate a positive association between 25(OH)D and the vascular sensitivity to AngII in obese hypertensives, and further suggest that vascular RAS activity may progressively increase when 25(OH)D deficiency occurs in obesity. Future studies to evaluate the effect of vitamin D supplementation on vascular RAS activity in obesity are needed.

The incidence of metabolic syndrome is rapidly increasing in the United States and worldwide. The metabolic syndrome is a complex metabolic and vascular disorder that is associated with inappropriate activation of the renin–angiotensin–aldosterone system (RAAS) in the cardiovascular (CV) system and increased CV morbidity and mortality. Insulin activation of the phosphatidylinositol-3-kinase (PI3K) pathway promotes nitric oxide (NO) production in the endothelium and glucose uptake in insulin-sensitive tissues. Angiotensin (Ang) II inhibits insulin-mediated PI3K pathway activation, thereby impairing endothelial NO production and Glut-4 translocation in insulin-sensitive tissues, which results in vascular and systemic insulin resistance, respectively. On the other hand, Ang II enhances insulin-mediated activation of the mitogen-activated protein kinase (MAPK) pathway, which leads to vasoconstriction and pathologic vascular cellular growth. Therefore, the interaction of Ang II with insulin signaling is fully operative not only in insulin-sensitive tissues but also in CV tissues, thereby linking insulin resistance and CV disease. This notion is further supported by an increasing number of experimental and clinical studies indicating that pharmacological blockade of RAAS improves insulin sensitivity and endothelial function, as well as reduces the incidence of new-onset diabetes in high-risk patients with CV disease. This article reviews experimental and clinical data elucidating the physiological and pathophysiological role of the interaction between insulin and RAAS in the development of insulin resistance as well as CV disease. [ABSTRACT FROM AUTHOR]