Abstract 151: The Effects of Obstructive Sleep Apnea on the Cerebral Vascular Wall
Obstructive sleep apnea (OSA) is a significant risk factor for stroke. However, little is known regarding how OSA affects the cerebrovascular wall. We hypothesized that (A) OSA will attenuate dilations of cerebral arteries by agonist-induced NO release from cerebrovascular endothelium and (B) OSA will upregulate endothelin-1 (ET-1)-mediated constrictions in cerebral arteries. Airway obstructions were induced by chronically implanting inflatable endotracheal obstruction devices (ODs). The ODs were remotely controlled by a computer to produce 30 apneas/hr (10 sec each) during 8 hrs of the sleep cycle in free-ranging rats. During apnea pO2 decreased from 122±3 to 67±3 mm Hg; pCO2 increased from 43±1 to 51±1 mm Hg; pH decreased from 7.46±0.00 to 7.38±0.01; and hemoglobin O2 saturation decreased from 94±1 to 82±1 % (n=5 and p<0.003 for each). After 4 weeks of apnea blood pressure in OSA rats were similar to that in sham rats (108±1 and 103±1 mmHg respectively). Cerebral arteries were isolated after 4 weeks from sham and OSA rats, mounted on pipettes, and pressurized. Diameter changes of the cerebral arteries were measured after the addition of various agents. Dilations to ATP, a P2Y2 agonist which stimulates NO production in the endothelium, were attenuated in cerebral arteries from OSA rats by 40% (n=5-8, P<0.05). However, the dilations to the NO donor, MAHMA-NOnoate, were similar between groups. Sensitivity to ET-1, an agonist for ETA and ETB, was increased ~20 fold in OSA arteries. EC50s for ET-1 constrictions in cerebral arteries from sham and OSA rats were 10.7 ± 4.3 nM and 0.5 ± 0.4 nM respectively (n=5-6, p=0.01). Constrictions to IRL-1620, a selective ETB agonist, were enhanced 11-fold in OSA compared to sham cerebral arteries (n=3-4, p<0.01). In preliminary studies, the increased sensitivity to ET-1in cerebral arteries from OSA rats was attenuated by the ETB antagonist, BQ-788. We conclude that OSA produces pathological changes involving decreased endothelial-derived NO production and enhances constrictor responses to ET-1 as a result of ETB upregulation. Since blood pressures were similar in the OSA and sham rats, we conclude that cerebrovascular dysfunction can occur with OSA in the absence of coexisting hypertension.
- © 2012 by American Heart Association, Inc.