Résumé
Abstract only Obstructive sleep apnea syndrome (OSA) is characterized by multiple breathing interruptions during sleep due to transient closing of the superior airways. This induces chronic intermittent hypoxia (IH), which enhances cardiovascular dysfunction and remodeling, potentially leading to hypertension and cardiac infarct. Since physical training has previously been described as limiting the extent and occurrence of several cardiovascular diseases, the aim of this study was to evaluate the beneficial effect of intensive training on the reactivity of arteries and calcium signaling in vascular smooth muscle cells (SMC) of rats submitted to IH. Four groups of Wistar rats were randomly assigned: N (normoxic sedentary rats), NIE (normoxic intensively exercised rats), IH (intermittent hypoxic sedentary rats) and IHIE (intermittent hypoxic intensively exercised rats). IH consisted in alternating normoxia (21%O 2 ) and hypoxia (5%O 2 ) every 30 sec in the cages for 8 h/day during 3 weeks. Exercise sessions were conducted 5 times/week in NIE and IHIE rats as a double fast 24 min walk with a speed progressively rising from 16 to 30 m/min. After 21 days of normoxia or IH (with/without training), the aortic ring tone in response to increasing doses of vasoactive agonists has been investigated by tension arteriography. Also, calcium imaging of cultured aortic SMC and protein expression of calcium channels were performed to examine the effects of lack of oxygen and/or training at the cellular and molecular levels respectively. 21 days of exposure to IH had no impact on the aortic response to tested vasoconstrictors (10 −11 to 10 −4 M endothelin‐1 and 10 −12 to 10 −5 M phenylephrine). IH also reduced by up to 20% the vasorelaxant effect of acetylcholine (at 10 −6 M), which is in accordance with the previously shown endothelial dysfunction generated by IH. On the contrary, intensive training increased by ~20% the vasodilatory effect of acetylcholine (10 −10 to 10 −3 M), compared to aortic responses of sedentary animals, while it decreased by ~50% the aortic response to the vasoconstrictors endothelin‐1 and phenylephrine in both normoxic and IH groups. Intensive training also increased the caffeine‐induced elevation of cytoplasmic calcium level in aortic SMC. At the molecular level, the protein expressions of major calcium channels like RyR or TRP were altered during hypoxia and/or exercise modulating SMC calcium signaling. Our results suggest that intensive exercise training could decrease the adverse effects of IH on the cardiovascular physiology trough calcium homeostasis. This could lead to improvements in the treatment of OSA patients. Support or Funding Information UGA, INSERM, Agir@Dom, AUF (PCSI)