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Background: The mechanism and markers of cardiovascular disease (CVD) in obstructive sleep apnea (OSA) remain unknown. The microcirculation is the site of early changes in OSA patients who are free of CVD risk., Methods: Patients with newly diagnosed moderate to severe OSA (n = 7) were studied before and 12 weeks after intensive treatment with continuous positive airway pressure (CPAP), along with weight and age matched controls (n = 7). Microcirculatory vessels were isolated from gluteal biopsies and changes in critical functional genes were measured., Results: The following genes changed after 12 weeks of intensive CPAP therapy in the microcirculatory vessels: angiotensin receptor type 1 (AGTR-1) (11.6 (3.4) to 6 (0.8); P = 0.019); NADPH oxidase (NOX4) (0.85 (0.02) to 0.79 (0.11); P = 0.016); and dimethylarginine dimethylaminohydrolase (DDAH 1) (1 (0.31) to 0.55 (0.1); P = 0.028). Despite decreased nitric oxide (NO) availability as measured indirectly through brachial artery flow-mediated dilation, endothelial NO synthase (NOS3) did not change with CPAP. Other disease markers of OSA that changed with treatment in the microcirculation were endothelin, hypoxia inducible factor 1a, nuclear factor kappa B, interleukin-8, and interleukin-6., Conclusions: In this ex vivo evaluation of the microcirculation of patients with OSA and no CVD risk, several pathways of CVD were activated supporting that OSA independently induces microcirculatory endothelial dysfunction and serving as disease-specific markers for future pharmacological targeting of OSA-related CVD risk. The findings support the role of renin-angiotensin activation and endothelial oxidative stress in the decreased microcirculatory NO availability in OSA., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Obstructive sleep apnea (OSA) is associated with vascular endothelial dysfunction (VED) in otherwise healthy patients. The role of renin-angiotensin system (RAS) in the OSA induced VED is not well understood., Methods: Recently diagnosed OSA patients with very low cardiovascular disease (CVD) risk (Framingham score <5%) were studied at diagnosis and after 12 weeks of verified continuous positive airway pressure (CPAP) therapy. Participants underwent biopsy of gluteal subcutaneous tissue at baseline and after CPAP. Microcirculatory endothelial expression of angiotensin receptors type-1 (AT-1) and type-2 (AT-2) was measured in the subcutaneous tissue using quantitative confocal microscopy techniques. The ex-vivo effect of AT-1 receptor blockade (ARB) on endothelial superoxide production was also measured before and after CPAP treatment., Results: In OSA patients (n = 11), microcirculatory endothelial AT1 expression decreased from 873 (200) (fluorescence units) at baseline to 393 (59) units after 12 weeks of CPAP (P = 0.02). AT2 expression did not decrease significantly in these patients (479 (75) to 329 (58) post CPAP (P = 0.08)). The ex-vivo addition of the losartan to the microcirculatory endothelium resulted in decreased superoxide expression in the vascular walls from 14.2 (2.2) units to 4.2 (0.8) P < 0.001; while it had no effect on post-CPAP patient tissue (P = 0.64)., Conclusions: In OSA patients with no to minimal CVD risk, VED is associated with upregulation of AT-1 expression that is reversible with CPAP. Endothelial oxidative stress was reversible with ARB. RAS activation may play an important role in the development of early CVD risk in OSA patients., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)