부산대학교 도서관

Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp[91.sup.phox]-containing NADPH oxidase in the development of left ventricular (LV) remodeling induced by intermittent hypoxic stress in mice. Male gp[91.sup.phox]-deficient (gp[91.sup.-/-] ) mice (n = 26) and wild-type (n = 39) mice at 7-12 wk of age were exposed to intermittent hypoxia (30 s of 4.5-5.5% [O.sub.2] followed by 30 s of 21% 02 for 8 h/day during daytime) or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic function were not changed by intermittent hypoxia in wild-type or gp[91.sup-/-] mice, although right ventricular systolic pressure tended to be increased. In wild-type mice, intermittent hypoxic stress significantly increased the diameter of cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore, intermittent hypoxic stress increased superoxide production, 4-hydroxy-2nonenal protein, TNF-[alpha] and transforming growth factor-[beta] mRNA, and NF-[kappa]B binding activity in wild-type, but not gp[91.sup.-/-], mice. These results suggest that gp[91.sup.phox]-containing NADPH oxidase plays a crucial role in the pathophysiology of intermittent hypoxia-induced LV remodeling through an increase of oxidative stress. oxidative stress; superoxide; cardiac hypertrophy; sleep apnea