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- Title
Exercise Attenuates Intermittent Hypoxia-Induced Cardiac Fibrosis Associated with Sodium-Hydrogen Exchanger-1 in Rats.
- Authors
Tsung-I Chen; Wei-Chia Tu
- 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.
- Subjects
HYPOXIA (Water); HEART fibrosis; SODIUM-hydrogen antiporter; LABORATORY rats; OXIDATIVE stress; OXIDANT status; SLEEP apnea syndrome treatment
- Publication
Frontiers in Physiology, 2016, Vol 7, p1
- ISSN
1664-042X
- Publication type
Article
- DOI
10.3389/fphys.2016.00462