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.

Hemorrhagic shock is a major cause of death in modern societies. Some patients, when treated, fail to sustain normal cardiovascular parameters, requiring fluid therapy and vasoactive drugs. Among drugs with cardiovascular profile other than catecholamine, vasopressin (VP) is emerging as an option. To better understand its effects during hemorrhagic shock, we compared the effects of VP and noradrenaline (NA), associated to fluid therapy. In this work, hamsters were subjected to shock by withdrawal of 40% of their blood volume and were then divided into five groups. One group was treated with saline solution, and the remaining ones with VP (three groups) and NA (one group) combined to fluid resuscitation. To assess receptor role, two more VP groups were pretreated with specific receptor blockers (anti-V1 or anti-V2, respectively) before its infusion. Microcirculatory parameters such as vessel diameter, red blood cell velocity, and functional capillary density were evaluated. In addition, blood gas analysis and lactate levels were also determined. Measurements were performed at baseline, after shock, and after treatment. At the end, leukocyte-endothelium interaction was evaluated, and animals were followed up to determine survival time. Neither saline solution nor NA recovered microcirculatory parameters, but VP treatment returned to near baseline values, except when V2 receptors were blocked. Functional capillary density was higher in the VP group after treatment, without statistical difference from baseline values. When V2 receptors were blocked, recovery was not achieved after treatment. The VP group also had a smaller number of adhering leukocytes and improved 72-h survival time compared with the NA one. This study suggests that, in hemorrhagic shock, treatment with low-dose VP, in combination with fluid therapy, improves tissue perfusion. This outcome is mediated mostly by V2 receptors, eliciting vasodilatation and consequently blood flow redistribution through the microcirculation.

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