Endothelial Dysfunction in the Microcirculation of Patients with Obstructive Sleep Apnea

Abstract

Rationale: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. We hypothesized that patients with OSA and no cardiovascular disease have oxidant-related microcirculatory endothelial dysfunction. Objectives: To evaluate the microcirculation in OSA. Methods: This study included seven patients with OSA and seven ageand weight-matched control subjects (mean age, 38 yr; mean body mass index, 32.5 kg/m 2 ). All participants were free of cardiovascular risk factors. Participants received measurement of brachial artery flow-mediated dilation and forearm subcutaneous biopsy. Patients underwent repeated tests 12 weeks after treatment. Microcirculatory endothelial cells were isolated, and immunohistochemistry staining for peroxynitrite in the microcirculation was performed. Measurements and Main Results: Flow-mediated dilation was lower in patients than in control subjects at baseline (mean 6 SEM: 5.7 6 0.5 vs. 9.5 6 0.6; P 5 0.02) and increased after treatment (5.7-7.3; change, 1.7 6 0.6; P 5 0.04). Microcirculatory peroxynitrite deposit was higher in patients compared with control subjects (44.0 6 1.6 vs. 21.8 6 1.9 stain density units; P , 0.001) and decreased after treatment from 44.0 to 30.5 stain density units (change, 213.5 6 2.9; P 5 0.009). In patients, transcription of endothelial nitric oxide synthase decreased from 5.2 to 21.3 after treatment (change, 6.5 6 2.5; P 5 0.05), and transcription of superoxide dismutase1 decreased from 24.0 to 212.3 after treatment (change, 28.3 6 2.1; P 5 0.01). These changes persisted after adjustment for weight and underlying severity of OSA. Conclusions: This is the first direct evaluation of the microcirculation in OSA. Patients with OSA with low cardiovascular risk status had increased oxidant production in the microcirculation and endothelial dysfunction, both of which improved with treatment. Endothelial nitric oxide synthase transcription decreased with treatment.

Endothelial function and sleep: Associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep

“…Thus, it is challenging to integrate our findings with the existing literature. Several studies suggest that FMD may be reduced among groups with disrupted sleep, such as adults doing night shift work and patients with confirmed OSA and (Amir et al,2004;Patt et al,2010), with other work reporting that patients with OSA who were treated with continuous positive airway pressure (CPAP) showed increased FMD (Panoutsopoulos et al,2012). The current study extends those findings by finding associations between sleep quality and FMD among non-shift working adults sampled from the general population, who did not have a previously diagnosed sleep disorder.…”

“…Studies suggest that certain populations known to have disrupted sleep, such as patients with diagnosed OSA and workers with night shift jobs, not only have higher risk for CVD (Wolk et al,2005;Wang et al,2011), but also have reduced endothelial function (Amir et al,2004;Patt et al,2010). However, little is known about how endothelial function, as measured by FMD, relates to sleep quality among the general population of adults.…”

Red Cell Distribution Width in Patients with Obstructive Sleep Apnea Syndrome

“…Both inflammation and oxidative stress have been known to play major roles in the pathogenesis of OSAS through CRP, IL-6, and other inflammatory markers and oxidative stress products [6,7,23,24,[35][36][37]. Through all of these pathways, inflammatory mediators, including cytokines such as TNFa or interleukin (IL)-1, IL-6, CRP, and chemokines such as IL-8 or monocyte chemoattractant protein-1 (MCP-1), and also through oxidative stress, OSAS has a potential link with cardiovascular diseases from the point of view of inflammation, atherosclerosis, and endothelial dysfunction [38,39]. RDW has been shown to have an association with cardiovascular diseases [14,40,41].…”

Audiologic profile of OSAS and simple snoring patients: the effect of chronic nocturnal intermittent hypoxia on auditory function

“…They evidenced increased peroxynitrite production in the microvascular walls of patients with OSAS, indicating overproduction of NO and superoxide in the endothelial environment. The uptake of NO by superoxide explains the decreased NO availability and the consequent microcirculatory changes which resulted independent of age, weight, or sex and reversible with treatment [36]. Similar mechanisms could be responsible of a progressive impairment of inner ear where the NO production by cochlear vascular cells causes smooth muscle and pericyte relaxation by the inhibition of voltage-gated calcium channels and the activation of ATP-sensitive K?…”