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Abnormal capillary permeability and endothelial dysfunction in hypertension with comorbid Metabolic Syndrome

      Abstract

      Purpose: Metabolic Syndrome as defined by ATP III criteria, a constellation of risk factors associated with insulin resistance, predisposes to premature atherosclerosis and early coronary events. Whether that negative risk profile is associated with endothelial dysfunction remains to be established. Materials and methods: Transcapillary escape rate of albumin (TERalb), a measure of capillary permeability and integrity of systemic capillary endothelium, and forearm vasodilation to intra-arterial acetylcholine (ACH), an index of nitric oxide (NO)-mediated vasomotor dysfunction, were assessed in 24 non-diabetic, uncomplicated hypertensive men with Metabolic Syndrome according to ATP III criteria (hypertension with at least two additional traits such as high triglycerides, low HDL, abdominal obesity, impaired fasting or post-load plasma glucose). Twelve age-matched lean normal hypertensive patients with normal lipid and glucose profile and nine normotensive subjects were the controls. All patients underwent lipids determination and fasting and post-OGTT insulin assessment; HOMA-IR was the index of insulin resistance. Results: TERalb was higher in hypertensive patients with Metabolic Syndrome, without differences between hypertensive and normotensive controls. Blood pressure (BP), lipids, plasma glucose, insulin levels and HOMA-IR were unrelated to TERalb. Responses to acetylcholine were selectively attenuated in metabolic patients and, on an individual basis, related only to HDL cholesterol levels, independent of LDL cholesterol, BP, body size, triglycerides, and HOMA-IR values. No relationship existed between responses to acetylcholine and TERalb. Conclusions: Altered systemic capillary permeability characterizes insulin-resistant hypertensive patients with Metabolic Syndrome. That defect, which may promote early atherosclerosis development, coexists with blunted endothelial-mediated vasodilation, indicating a pervasive abnormality of endothelial function.

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