title: Role of Sodium-Hydrogen Exchanger-1 (NHE-1) in the Effect of Exercise on Intermittent Hypoxia-Induced Left Ventricular Dysfunction.
abstract: Intermittent hypoxia (IH) occurs frequently in patients with obstructive sleep apnoea and can cause ventricular dysfunction. However, whether myocardial inflammation and sodium-hydrogen exchanger-1 (NHE-1) expression play an important role in IH-induced ventricular dysfunction remains unclear. This study aimed to investigate whether short-term exercise provides a protective effect on IH-induced left ventricular (LV) function impairment. Male Sprague-Dawley rats were randomly assigned to 4 groups: control (CON), IH, exercise (EXE) or IH interspersed with EXE (IHEXE). IH rats were exposed to repetitive hypoxia/reoxygenation cycles (2%-6% O₂ for 2-5 s per 75 s, followed by 21% O₂ for 6 h/day) during the light phase for 12 consecutive days. EXE rats were habituated to treadmill running for 5 days, permitted 2 days of rest, and followed by 5 exercise bouts (30 m/min for 60 min on a 2% grade) on consecutive days during the dark phase. IHEXE rats were exposed to IH during the light phase interspersed with exercise programs during the dark phase on the same day. Cardiac function was quantified by echocardiographic evaluation. Myocardial levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and NHE-1 were determined. IH rats showed LV dysfunction characterized by lower LV fractional shortening (LVFS%) and LV ejection fraction (LVEF%). LV dysfunction was associated with higher myocardial levels of TNF-α, IL-6 and NHE-1 mRNA and protein. These changes were not observed in IHEXE rats (P > 0.05 for all). EXE rats showed lower levels of NHE-1 protein than CON rats (P < 0.05). However, the levels of LVFS%, LVEF%, TNF-α and IL-6 protein and NHE-1 mRNA did not differ between EXE and CON rats (P > 0.05 for all). These data indicated that exercise may provide a protective effect on IH-induced LV dysfunction by attenuating IH-induced myocardial NHE-1 hyperactivity.
authors.affiliation: Department of Cardiology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan, Republic of China.|PhD Program in Institute of Medicine, Tzu Chi University, Hualien 97004, Taiwan, Republic of China.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Chen M
authors.affiliation: Department of Physiology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan, Republic of China.
authors.forename: Kun-Ta
authors.initials: KT
authors.lastname: Yang
authors.affiliation: PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien 97004, Taiwan, Republic of China.
authors.forename: Yan-Jhih
authors.initials: YJ
authors.lastname: Shen
authors.affiliation: Department of Pediatrics, Tzu Chi University, Hualien 97004, Taiwan, Republic of China.|Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan, Republic of China.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.affiliation: Master program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan, Republic of China.
authors.forename: Wei-Chia
authors.initials: WC
authors.lastname: Tu
authors.affiliation: Center of Physical Education, Tzu Chi University, Hualien 97004, Taiwan, Republic of China.
authors.forename: Tsung-I
authors.initials: TI
authors.lastname: Chen
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000150:complications*; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*
chemical_list: D015850:Interleukin-6; D017923:Sodium-Hydrogen Exchangers; D014409:Tumor Necrosis Factor-alpha; C069139:growth factor-activatable Na-H exchanger NHE-1