Intensive physical training reduces intermittent hypoxia‐related vascular dysfunction by affecting the mechanisms of smooth muscle from molecular to physiological scales
Authors: ESTEVE Eric Jean‐Claude , El Dirani Zeinab , Chaouni Samia , Lemarie Emeline , Joumaa Wissam , Daher Ahmad , Leclercq‐Samson Adeline , Faury Gilles 
Published: June 2021

Obstructive sleep apnea syndrome (OSA) is a common clinical condition produced by episodes of repeated upper airways obstruction resulting in airflow blockade (apnea) during sleep. OSA is defined as a frequent chronic disease, which is highly prevalent in the population (affecting 9% of women and 24% of men) and which increases linearly with age. Chronic intermittent hypoxia (IH), the main pathogenic consequence related to OSA, is responsible for cardiovascular morbidity, including systemic arterial hypertension, cardiac infarct, atherosclerosis, and muscular remodeling in OSA patients.Systemic hypertension is the first cardiovascular disease related to OSA, thus 50% to 90% of patients with OSA develop hypertension. The mechanisms by which intermittent hypoxia induces the hypertension are not fully explained; we still don't know exactly the cause of hypertension, which make it a difficult medical condition to control, and make standard pharmacological interventions ineffective. Thus in order to found an effective treatment for hypertension induced by IH, we have to seek a non‐pharmacological intervention.While IH is known to contribute to hypertension, physical intensive training (IT) wields beneficial effects on the cardiovascular system and is known to reduce the hypertension risk in adults. Since physical exercise decreases the risk of cardiovascular events, the magnitude of this benefit can be also used as an anti‐hypertensive intervention.We choses a high‐intensity exercise protocol (exercise sessions during 21 days, 5 times/week on rats as a double fast 24 min‐walk with a speed progressively rising from 16 to 30 m/min), to prevent the IH‐impact and examine if IT can reverse or reduce the deleterious effects of IH (alternating normoxia (21%O2) and hypoxia (5%O2) every 30 sec in the cages for 8 h/day during 3 weeks) on the vascular reactivity, muscular remodeling and prevents the occurrence of hypertension.As expected, we found beneficial effects of training on physiological parameters (heart rate, arterial pressure), but also on vascular remodeling of several vessels (thoracic, abdominal, carotidal and pulmonary arteries); in addition we were able to observe opposite effects between IH and IT on gene transcription (Q‐PCR) and protein production (western blot) of several channels associated to calcium signaling (e.g. RyR, IP3R, SERCA, TRP) in cardiovascular system. We also compared calcium transient (ΔF/F0) from sarcoplasmic reticulum between normoxic and hypoxic smooth muscle cells and the significant difference (respectively 0,69±0,15 vs 1,01±0,21, p<0,05) was abolished in cells from trained rats. Taken together, these results suggest that IT could decrease the adverse effects of IH on the cardiovascular system by acting from molecular to physiological organizations of muscular tissue. These data support the hypothesis that intensive exercise training may represent a promising non‐invasive, non‐pharmacological and complementary approach for the treatment of systemic hypertension.Support or Funding InformationINSERM, University of Grenoble Alps, University of Lebanon, AUF (PCSI)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.