Chronic intermittent hypoxia exacerbates oxidative stress and deteriorates calcium homeostasis in rat hearts

Poster Presentations: P113OBJECTIVES: In our study we hypothesized that chronic intermittent hypoxia mimicking obstructive sleep apnea aggravates oxidative stress and impairs calcium (Ca2+) -handling in rat cardiac myocytes. METHODS: Adult male 2-month old Sprague-Dawley rats were daily administered with melatonin (MIH, 10mg/Kg/day of body weight, i.p.) or vehicle (VIH, 2% ethanol in normal saline) and exposed to intermittent hypoxic chamber (inspired oxygen alternating from 21 to 5 +/- 0.5% oxygen per minute for 8 hr/day) for 28 days. Levels of malodialdehyde (MDA) and the mRNA expressions of anti-oxidant enzymes in all rat hearts were determined by colorimetric study and reverse transcription-PCR respectively. Impairments of sarcoplasmic reticulum (SR) Ca2+ -handling were measured by spectrofluorometer in isolated fura-2-loaded ventricular myocytes from all rat groups. And the differences in protein expressions and activities of SR - Ca2+ handling proteins were measured by western blot and 45Ca2+ flux study in the ventricular myocytes from all rat groups. RESULTS: The ratio of heart weight to body weight and the production of MDA were significantly more in VIH group than that of normoxic and MIH groups. In addition, the mRNA levels of catalase and Mn-superoxide dismutase in VIH group were much less than that of other two groups. Moreover, spectroflurometric studies showed that decreases in SR - Ca2+ content and the metabolic inhibition/anoxia induced intracellular Ca2+ overload were much remarkable in VIH ventricular myocytes compared to the normoxic control. Also the protein levels and activities of SR Ca2+ -ATPase and sarcolemmal Na+ - Ca2+ exchanger were markedly reduced in VIH cardiomyocytes. However, those impairments were significantly ameliorated in MIH group. CONCLUSIONS: In this study we show that chronic intermittent hypoxia leading to myocardial injuries by severe oxidative stress and impairments of SR Ca2+ handling in rat cardiomyocytes