Year: 2010
Type: dissertation
Abstract: Obstructive Sleep Apnea (OSA) is a risk factor for cardiovascular diseases. Patients with OSA have endothelial dysfunction and reduced Nitric Oxide (NO∙) bioavailability. The expression of endothelial NO∙ synthase (eNOS) in patients with OSA has not been evaluated. Additionally, increased superoxide in the vascular environment may interact with NO∙ producing peroxynitrite, thereby reducing the available NO∙. Patients with OSA (AHI >15) and no clinically manifested cardiovascular disease along with healthy controls were enrolled. Volunteers(n=7) underwent measurement of flow mediated dilation (FMD) of the brachial artery for assessment of NO∙ dependent endothelial function. Patients returned 10-12 weeks after treatment for a repeat FMD. Percutaneous biopsy was taken from the forearm of patients for measurement of eNOS activity at baseline and conclusion and for nitrotyrosine staining. Endothelial cells were extracted by Laser Microdisection Pressure Catapulting. eNOS expression pre and post treatment was controlled to endogenous b-actin and 18s rRNA primers. Immunohistochemical staining for peroxynitrite was done with an anti-nitrotyrosine antibody stain. Slides were scanned digitally and analyzed by a blinded observer using imaging software. At baseline, OSA patients had FMD of 5.7% (0.5) vs. 9.7% (0.6) in controls(p<0.001). Post treatment FMD increased to 7.3% (0.0) (p<0.04). Average Nitrotyrosine Stain density ratio was 44.0(1.6) in OSA patients vs. 21.8 (1.9) in controls (p<0.001) and decreased following treatment to 30.5 (2.3) (p<0.01 vs. pre). At baseline, eNOS expression ( ΔCt) was 5.2 fold more than control and decreased post-treatment to -1.3 fold with a difference of -6.5 (2.5) (p<0.05). Expression of SOD-1 also decreased with treatment with a difference of -8.3 (2.1) ΔCt. p=0.011 After 10-12 weeks of treatment, patients with OSA had an improvement in their endothelial function. The improvement in endothelial function was associated with reduced scavenging of NO by super oxide. eNOS levels were elevated at baseline and reduced with treatment. Endothelial dysfunction in OSA is not associated with reduced eNOS activity.
Author: Diane N. Haddad
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W66510056