Increment of body mass index is positively correlated with worsening of endothelium-dependent and independent changes in forearm blood flow

Abstract

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. As obesity is a multiple grade disease, we have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones, creating a window of opportunities for preventive measures. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls (n = 9); Overweight (n = 11); Obese class I (n = 26); Obese class II (n = 15); Obese class III (n = 19). Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Known determinants of endothelial dysfunction, such as inflammatory response, insulin resistance, and diagnosis of metabolic syndrome, did not correlate with forearm blood flow response to vasodilators. Moreover, several risk factors for atherosclerosis were excluded as independent predictors after confounder-adjusted analysis. Our data suggests that obesity per se could be sufficient to promote impairment of vascular reactivity, that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected, and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow.

Methods of Endothelial Function Assessment: Description and Applications

“…When the response is consistent with the stimulus, the endothelial function is preserved. 43 Invasive VOP, i.e., involving intra-arterial infusion of vasoactive substances, is considered a gold standard tool for analysis of vascular behavior, but is largely impractical in the clinical setting.…”

“…This is measured by a strain gauge, which detects any change in tissue volume, placed in the point of maximal circumference of the forearm. 43 At resting conditions, blood flow in the forearm is divided into 70% in striated skeletal muscle and 30% in the skin. There are multiple arteriovenous communications in the hand related to skin supply.…”

“…Usually, increasing doses of ACh are administered during 5 minutes and the forearm blood flow is measured (as mL.100mL -1 .min -1 ) in the last two minutes of infusion. 43,47 Endothelium-independent vasodilation is evaluated by the infusion of vasoactive substances that act as NO precursors, such as sodium nitroprusside, for example. Vascular changes will be detected by strain gauges, which confirm whether an adequate response has occurred.…”

“…41,42 For its easy applicability, VOP has been widely used in in vivo studies on vascular physiology in humans, both in healthy individuals and in several disease conditions. 43 VOP is a non-invasive method that involves inflation of the upper arm cuff to a pressure lower than systolic pressure. Usually, an inflation pressure of around 40 mmHg is used for intervals of approximately 10 seconds, followed by 5 seconds of deflation, during 2-3 minutes 44,45 The inflation pressure used is sufficient to arrest venous return without impairing arterial flow towards the forearm, causing a linear increase in blood flow to the limb.…”

“…To avoid that such blood supply affects the measurement of forearm blood flow, a wrist cuff is inflated to suprasystolic pressure just before flow measurement. 42,43,46,47 Vessel responsiveness is assessed by evaluation of volume changes in the limb in response to stimuli, which can be a mechanical stimulus that promotes reactive hyperemia, or a chemical stimulus via administration of vasoactive compounds (invasive technique). A decreased or impaired response may be an evidence of endothelial dysfunction, 48 which is considered a critical factor for the development, progression and complications of coronary artery disease.…”