Effect of chronic continual- and intermittent hypoxia-induced systemic inflammation on the cardiovascular system in rats.
OBJECTIVE
Obstructive sleep apnea syndrome (OSAS) has been recognized as an important risk factor for cardiovascular morbidity and mortality. However, the underlying mechanisms are poorly understood. Present study aimed to investigate the role of NF-κB-dependent inflammation pathways in pathophysiological responses of cardiovascular system in OSAS.


METHODS
Thirty male specific pathogen-free (SPF) Sprague-Dawley rats were randomly assigned to normoxia (N) group, continual hypoxia (CH) group, and intermittent hypoxia (IH) group (n = 10) and were exposed to N (21% O2), CH (8% O2), or IH (6-11% O2 for 10 s and 21% O2 for 80 s in every 90 s) for 8 h/day for 35 days. The hemodynamic and pathomorphologic effects of IH and CH exposure were investigated as well as the expression of NF-κB-dependent inflammation factors.


RESULTS
Chronic IH or CH significantly increased mean pulmonary arterial pressure (mPAP) in rats, while no significant changes occurred in mean carotid arterial pressure (mCAP). The ratio of right ventricle (RV) to left ventricle (LV) + septum (S) was significantly increased by both IH and CH, suggesting RV hypertrophy was induced by IH or CH. Elastic fiber staining showed an irregular pattern of elastic fiber distribution after hypoxia, and aortic tunica media thickness was increased. Both chronic IH and CH upregulated the expressions of transcription factor NF-κB and related pro-inflammatory cytokines and adhesion molecules.


CONCLUSIONS
The current study expands our understanding that both IH and CH could activate the expression of NF-κB and related inflammatory factors as well as cause pathophysiologic damage to the cardiovascular system in OSAS. All these results provide further support to an emerging hypothesis that activation of NF-κB-dependent inflammation may play a central role in the pathophysiology of cardiovascular dysfunction in OSAS.
Key Laboratory of Heart and Lung, Wenzhou & Department of Respiratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Xiao-Mei
XM
Xu
Dan
D
Yao
Xue-Ding
XD
Cai
Cheng
C
Ding
Qian-Ding
QD
Lin
Liang-Xing
LX
Wang
Xiao-Ying
XY
Huang
D000818:Animals; D001011:Aorta / Q000473:pathology; D002318:Cardiovascular Diseases / Q000473:pathology* / Q000503:physiopathology*; D002319:Cardiovascular System / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D016328:NF-kappa B / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020181:Sleep Apnea, Obstructive / Q000473:pathology / Q000503:physiopathology*
D018836:Inflammation Mediators; D016328:NF-kappa B