HIIT and MICT on Nitric Oxide-mediated Erythrocyte Rheology

Exercise Clinical Trial

Official title:

Effects of High Intensity Interval Training and Moderate Intensity Continuous Training on Nitric Oxide-mediated Erythrocyte Rheology

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04823429
• Other study ID #: 202000448A3
• Status: Recruiting
• Phase: N/A
• Start date: March 5, 2021
• Est. completion date: September 4, 2021

Study information

• Verified date: March 2021
• Source: Chang Gung Memorial Hospital
• Contact: Jong-Shyan Wang, PhD
• Phone: +886-3-2118800
• Email: s5492[@]mail.cgu.edu.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 4, 2021
• Est. primary completion date: September 4, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Exercise
• Interval Training

Intervention

Behavioral:
• High intensity-interval training (HIIT)
Subjects performed HIIT (3-min intervals at 40% and 80%VO2peak) on a bicycle ergometer for 30 min/day, 5 days/week for 6 weeks. Without any exercise training
• Moderate intensity-continuous (MICT)
Subjects performed MICT (sustained 60%VO 2max) on a bicycle ergometer for 30 min/day, 5 days/week for 6 weeks.

Locations

Country	Name	City	State
Taiwan	Chang Gung University	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (6)

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. Review. — View 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. — View 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. — View 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. — View Citation

Suhr F, Brenig J, Müller 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intracellular NO production response to exercise training.	Added different inhibitors or agonists to investigate the effects of exercise training on NO production mediated by eNOS-NO pathway.	8 weeks
Primary	Intracellular ROS production response to exercise training.	Added different inhibitors or agonists to investigate the effects of exercise training on ROS production mediated by eNOS-NO pathway.	8 weeks
Primary	The levels of eNOS, p-eNOS and Band-3 response to exercise training.	Detect the following protein levels: eNOS, p-eNOS and Band-3, by the western blots.	8 weeks
Secondary	Determination of erythrocyte biological markers by Flow Cytometry	Using the Flow Cytometry to detect the following markers: CD242, CD239, NADPH oxidase 2 (Nox2) and Arginase 1 (Arg1).	8 weeks
Secondary	Erythrocyte deformability	Isolated erythrocyte first, then assess erythrocyte deformability (elongation index ) by using laser assisted optical rotational red cell analyzer (LoRRca).	8 weeks
Secondary	Cardiopulmonary fitness	To assess cardiopulmonary fitness, cardiopulmonary exercise test (CPET) on a cycle ergometer was performed 4 days before and after the intervention. All subjects underwent exercise with a mask to measured oxygen consumption (VO2) breath by breath using a computer-based system.	8 weeks