Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea

Brian T. Patt, David Jarjoura, Diane N. Haddad, Chandan K. Sen, Sashwati Roy, Nicholas A. Flavahan, Rami N. Khayat

Research output: Contribution to journalArticlepeer-review

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/m2). 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 ± SEM: 5.7 ± 0.5 vs. 9.5 ± 0.6; P = 0.02) and increased after treatment (5.7-7.3; change, 1.7 ± 0.6; P = 0.04). Microcirculatory peroxynitrite deposit was higher in patients compared with control subjects (44.0 ± 1.6 vs. 21.8 ± 1.9 stain density units; P < 0.001) and decreased after treatment from 44.0 to 30.5 stain density units (change, -13.5 ± 2.9; P = 0.009). In patients, transcription of endothelial nitric oxide synthase decreased from 5.2 to -1.3 after treatment (change, 6.5 ± 2.5; P = 0.05), and transcription of superoxide dismutase1 decreased from -4.0 to -12.3 after treatment (change, -8.3 ± 2.1; P = 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 improvedwith treatment. Endothelial nitric oxide synthase transcription decreased with treatment.

Original languageEnglish (US)
Pages (from-to)1540-1545
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume182
Issue number12
DOIs
StatePublished - Dec 15 2010

Keywords

  • Endothelial function
  • Microcirculation
  • Obstructive sleep apnea

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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