TY - JOUR
T1 - Endothelial nitric oxide synthase uncoupling
T2 - A novel pathway in OSA induced vascular endothelial dysfunction
AU - Varadharaj, Saradhadevi
AU - Porter, Kyle
AU - Pleister, Adam
AU - Wannemacher, Jacob
AU - Sow, Angela
AU - Jarjoura, David
AU - Zweier, Jay L.
AU - Khayat, Rami N.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2•-) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor l-Nitroarginine-Methyl-Ester (l-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2•- and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2•- overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA.
AB - The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2•-) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor l-Nitroarginine-Methyl-Ester (l-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2•- and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2•- overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA.
KW - Endothelial dysfunction
KW - Hypertension
KW - Nitric oxide
KW - Obstructive sleep apnea
UR - http://www.scopus.com/inward/record.url?scp=84920453525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920453525&partnerID=8YFLogxK
U2 - 10.1016/j.resp.2014.12.012
DO - 10.1016/j.resp.2014.12.012
M3 - Article
C2 - 25534145
AN - SCOPUS:84920453525
SN - 1569-9048
VL - 207
SP - 40
EP - 47
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
ER -