Endothelial nitric oxide synthase uncoupling: A novel pathway in OSA induced vascular endothelial dysfunction

Saradhadevi Varadharaj, Kyle Porter, Adam Pleister, Jacob Wannemacher, Angela Sow, David Jarjoura, Jay L. Zweier, Rami N. Khayat

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalRespiratory Physiology and Neurobiology
Volume207
DOIs
StatePublished - Feb 1 2015
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Obstructive Sleep Apnea
Blood Vessels
Endothelium
Nitric Oxide
Nitroarginine
Therapeutics
Confocal Microscopy
Superoxides
Esters
Cardiovascular Diseases
Biopsy

Keywords

  • Endothelial dysfunction
  • Hypertension
  • Nitric oxide
  • Obstructive sleep apnea

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Neuroscience(all)

Cite this

Endothelial nitric oxide synthase uncoupling : A novel pathway in OSA induced vascular endothelial dysfunction. / Varadharaj, Saradhadevi; Porter, Kyle; Pleister, Adam; Wannemacher, Jacob; Sow, Angela; Jarjoura, David; Zweier, Jay L.; Khayat, Rami N.

In: Respiratory Physiology and Neurobiology, Vol. 207, 01.02.2015, p. 40-47.

Research output: Contribution to journalArticle

Varadharaj, S, Porter, K, Pleister, A, Wannemacher, J, Sow, A, Jarjoura, D, Zweier, JL & Khayat, RN 2015, 'Endothelial nitric oxide synthase uncoupling: A novel pathway in OSA induced vascular endothelial dysfunction', Respiratory Physiology and Neurobiology, vol. 207, pp. 40-47. https://doi.org/10.1016/j.resp.2014.12.012
Varadharaj, Saradhadevi ; Porter, Kyle ; Pleister, Adam ; Wannemacher, Jacob ; Sow, Angela ; Jarjoura, David ; Zweier, Jay L. ; Khayat, Rami N. / Endothelial nitric oxide synthase uncoupling : A novel pathway in OSA induced vascular endothelial dysfunction. In: Respiratory Physiology and Neurobiology. 2015 ; Vol. 207. pp. 40-47.
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