title: Exercise Attenuates Intermittent Hypoxia-Induced Cardiac Fibrosis Associated with Sodium-Hydrogen Exchanger-1 in Rats.
abstract: Purpose:To investigate the role of sodium-hydrogen exchanger-1 (NHE-1) and exercise training on intermittent hypoxia-induced cardiac fibrosis in obstructive sleep apnea (OSA), using an animal model mimicking the intermittent hypoxia of OSA.Methods:Eight-week-old male Sprague-Dawley rats were randomly assigned to control (CON), intermittent hypoxia (IH), exercise (EXE), or IH combined with exercise (IHEXE) groups. These groups were randomly assigned to subgroups receiving either a vehicle or the NHE-1 inhibitor cariporide. The EXE and IHEXE rats underwent exercise training on an animal treadmill for 10 weeks (5 days/week, 60 min/day, 24-30 m/min, 2-10% grade). The IH and IHEXE rats were exposed to 14 days of IH (30 s of hypoxia-nadir of 2-6% O2-followed by 45 s of normoxia) for 8 h/day. At the end of 10 weeks, rats were sacrificed and then hearts were removed to determine the myocardial levels of fibrosis index, oxidative stress, antioxidant capacity, and NHE-1 activation.Results:Compared to the CON rats, IH induced higher cardiac fibrosis, lower myocardial catalase, and superoxidative dismutase activities, higher myocardial lipid and protein peroxidation and higher NHE-1 activation (p< 0.05 for each), which were all abolished by cariporide. Compared to the IH rats, lower cardiac fibrosis, higher myocardial antioxidant capacity, lower myocardial lipid, and protein peroxidation and lower NHE-1 activation were found in the IHEXE rats (p< 0.05 for each).Conclusion:IH-induced cardiac fibrosis was associated with NHE-1 hyperactivity. However, exercise training and cariporide exerted an inhibitory effect to prevent myocardial NHE-1 hyperactivity, which contributed to reduced IH-induced cardiac fibrosis. Therefore, NHE-1 plays a critical role in the effect of exercise on IH-induced increased cardiac fibrosis.
authors: Center of Physical Education, Office of General and Basic Education, Tzu Chi University Hualien, Taiwan.
authors: Tsung-I
authors: TI
authors: Chen
authors: Master program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University Hualien, Taiwan.
authors: Wei-Chia
authors: WC
authors: Tu
keywords: anti-fibrosis; antioxidant capacity; fibrosis; heart; intermittent hypoxia; obstructive sleep apnea; oxidative stress; sodium hydrogen exchanger