Clinical trial NCT04823429: HIIT and MICT on Nitric Oxide-mediated Erythrocyte Rheology
Official title: Effects of High Intensity Interval Training and Moderate Intensity Continuous Training on Nitric Oxide-mediated Erythrocyte Rheology
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Exercise
Interval Training
Keywords: Erythrocyte
eNOS
High intensity interval training
deformability
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2021-03-30
Enrollment: 60
Sex: MALE
Minimum age (years): 20
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Erythrocyte rheological properties affect blood viscoelasticity and consequently regulate vascular resistance to flow shear force, whereas rheological impairments of erythrocytes may result in circulatory disorders. The aim of this study was to establish an effective exercise strategy for improving individual aerobic capacity and for simultaneously ameliorating the risk of hemorheological dysfunction evoked by a graded exercise test (GXT) and the hypotheses is exercise intervention will improved hemorheological functions by enhancing deformability of erythrocytes via NO-mediated mechanism. This study included 60 healthy sedentary mens (age 20\~30) from Chang Gung university than were randomized into the HIIT \[3-min intervals at 40% and 80% V̇O2 reserve (V̇O2R),n=10\] and MICT(sustained 60% V̇O2R,n=10)on a bicycle ergometer for 30min·d-1, 5 d·wk-1 for 6 wk.

Detailed description: Recently, the role of erythrocyte has been more emphasized, which also related with endothelial cell. For coronary artery patients, the endothelial nitric oxide synthase activity in red blood cell (RBC-eNOS activity) is lower than age-matched health people, and it is related with dysfunction of endothelial cell. In cardiovascular diseases. the erythrocyte arginase-1 is active and seize L-arginine with eNOS. When the Arg-1 stimulated by reactive oxygen species (ROS), the nitric oxide (NO) bioactivity decrease and produce more ROS, meanwhile, ROS can go around to stimulate Arg-1. When the RBC-NO production is lowering, it will increase the adhesion activity to endothelial cell due to erythrocyte can be quite close to blood vessel well then release Nitric Oxide, induce the dysfunction and oxidative pressure of endothelial cell. The NO can also regulate the deformability of erythrocytes, and extremely affect oxygen supply to tissue once the deformability and aggregation of erythrocyte become abnormal. Besides NO, the deformability will be affected if erythrocyte is continuously exposed to the endogenous or exogenous ROS, which also increase adhesion to endothelial cell with the exposure of phosphatidylserine. Exercise can regulate the mechanism of NO release from erythrocyte, affecting the rheology of erythrocyte, and improve the anti-oxidation ability. Therefore, as mentioned above which make erythrocyte, as many aspects, become an important role on atherosclerosis disease treatment.

Eligibility criteria: Inclusion Criteria:

* Having a sedentary lifestyle (without regular exercise, exercise frequency ≤ once weekly, duration \< 20 min).

Exclusion Criteria:

* Exposed to high altitudes (\> 3000 m) for at least 1 year.
* Smoker
* Taking medications or vitamins
* Having any cardiopulmonary/hematological risk.

Primary outcomes:
measure: Intracellular NO production response to exercise training.
timeFrame: 8 weeks
measure: Intracellular ROS production response to exercise training.
timeFrame: 8 weeks
measure: The levels of eNOS, p-eNOS and Band-3 response to exercise training.
timeFrame: 8 weeks
Secondary outcomes:
measure: Determination of erythrocyte biological markers by Flow Cytometry
timeFrame: 8 weeks
measure: Erythrocyte deformability
timeFrame: 8 weeks
measure: Cardiopulmonary fitness
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung University
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Jong-Shyan Wang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mao TY, Fu LL, Wang JS. Hypoxic exercise training causes erythrocyte senescence and rheological dysfunction by depressed Gardos channel activity. J Appl Physiol (1985). 2011 Aug;111(2):382-91. doi: 10.1152/japplphysiol.00096.2011. Epub 2011 May 5.
citation: Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Nielsen S. Aquaporin water channels--from atomic structure to clinical medicine. J Physiol. 2002 Jul 1;542(Pt 1):3-16. doi: 10.1113/jphysiol.2002.020818.
citation: Wang JS, Fu TC, Lien HY, Wang CH, Hsu CC, Wu WC, Chien YW, Cherng WJ. Effect of aerobic interval training on erythrocyte rheological and hemodynamic functions in heart failure patients with anemia. Int J Cardiol. 2013 Sep 30;168(2):1243-50. doi: 10.1016/j.ijcard.2012.11.053. Epub 2012 Nov 27.
citation: Chou SL, Huang YC, Fu TC, Hsu CC, Wang JS. Cycling Exercise Training Alleviates Hypoxia-Impaired Erythrocyte Rheology. Med Sci Sports Exerc. 2016 Jan;48(1):57-65. doi: 10.1249/MSS.0000000000000730.
citation: Grau M, Pauly S, Ali J, Walpurgis K, Thevis M, Bloch W, Suhr F. RBC-NOS-dependent S-nitrosylation of cytoskeletal proteins improves RBC deformability. PLoS One. 2013;8(2):e56759. doi: 10.1371/journal.pone.0056759. Epub 2013 Feb 12.
citation: Suhr F, Brenig J, Muller R, Behrens H, Bloch W, Grau M. Moderate exercise promotes human RBC-NOS activity, NO production and deformability through Akt kinase pathway. PLoS One. 2012;7(9):e45982. doi: 10.1371/journal.pone.0045982. Epub 2012 Sep 25.