Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea.
BACKGROUND
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.


OBJECTIVE
To evaluate the microcirculation in OSA.


METHODS
This study included seven patients with OSA and seven age- and 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.


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 improved with treatment. Endothelial nitric oxide synthase transcription decreased with treatment.
Patt
Brian T
BT
The Ohio State University Columbus, USA.
Jarjoura
David
D
Haddad
Diane N
DN
Sen
Chandan K
CK
Roy
Sashwati
S
Flavahan
Nicholas A
NA
Khayat
Rami N
RN
D000328:Adult; D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D020181:Sleep Apnea, Obstructive / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1; D018615:Ultrasonography, Doppler, Color; D014664:Vasodilation / Q000502:physiology*
C000606290:SOD1 protein, human; D012313:RNA; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1