Compare the Effect of Eight Weeks of Resistance Training with and without Blood Flow Restriction on Nitric Oxide and Endothelin-1 Levels in Inactive Men with Prehypertension: A Simple Randomized Clinical Trial

Document Type : Original Articles

Authors
Ali Yari 1
Sedigheh Hosseinpour-Delavar 2
Ali Zabet 3
1 PhD Student, Department of Exercise Physiology, Ker.C., Islamic Azad University, Kermanshah, Iran
2 Associate Professor, Department of Exercise Physiology, Ker.C., Islamic Azad University, Kermanshah, Iran
3 Assistant Professor, Department of Exercise Physiology, Kan.C., Islamic Azad University, Kangavar, Iran
10.48305/jrrs.2026.46151.1137
Abstract
Introduction: Prehypertension is associated with endothelial dysfunction and a disrupted balance of vascular mediators. Resistance training with blood flow restriction (BFR) has emerged as a novel strategy for improving vascular indices. The present study aimed to investigate the effects of 8 weeks of resistance training, with and without BFR, on nitric oxide (NO) and endothelin-1 (ET-1) levels in sedentary men with prehypertension.
Materials and Methods: A total of 36 sedentary young men with prehypertension were randomly assigned to one of three groups: a control group (CON), a resistance training with blood flow restriction group (RT+BFR), and a resistance training without blood flow restriction group (RT). The training intervention was conducted over eight weeks. Systolic and diastolic blood pressure, as well as NO and ET‑1 plasma levels, were measured 48 hours prior to and 48 hours following the intervention. Data were analyzed using a paired-sample T-test and analysis of covariance (ANCOVA), with a Bonferroni post hoc correction applied at P ≤ 0.05.
Results: Both resistance training modalities (with and without BFR) produced significant increases in NO levels compared to the control group (P = 0.001 and P = 0.006, respectively) and significant reductions in ET‑1 concentrations (P = 0.001 and P = 0.003, respectively). Blood pressure also improved significantly in both experimental groups. However, no significant differences were observed between the two resistance training modalities with respect to NO (P = 0.123), ET‑1 (P = 0.571), or blood pressure levels.
Conclusion: Low-intensity resistance training combined with BFR improves endothelial mediators and blood pressure to levels comparable to those achieved with traditional high-intensity resistance training. This approach may therefore serve as an effective, mechanically less demanding exercise alternative for enhancing vascular health in men with prehypertension.
Keywords
Prehypertension
Resistance training
Blood flow restriction
Nitric oxide
Endothelin-1
Subjects
1.     Wang Z, Chen D, Peng L, Wang X, Ding Q, Li L, Xu T. Serum γ-glutamyltransferase levels and obesity status changes the risk of prehypertension in Chinese adults. Preventive Medicine Reports. 2024; 43: 102792.
2.     Kota V, Kumar S, Acharya S. Lifestyle modification and nutrition in preventing prehypertension and hypertension—narrative review. International Journal of Nutrition, Pharmacology, Neurological Diseases. 2023; 13(1): 9–15.
3.     Pescatello LS, Buchner DM, Jakicic JM, Powell KE, Kraus WE, Bloodgood B, Campbell WW, Dietz S, DiPietro L, George SM, Macko RF. Physical activity to prevent and treat hypertension: a systematic review. Medicine & Science in Sports & Exercise. 2019; 51(6): 1314–23.
4.     Ferreira Mendes B, Improta-Caria AC, Diniz e Magalhães CO, Dias Peixoto MF, Cardoso Cassilhas R, de Oliveira EM, De Sousa RA. Resistance training reduces blood pressure: putative molecular mechanisms. Current Hypertension Reviews. 2024; 20(1): 52–6.
5.     Młynarska E, Bojdo K, Frankenstein H, Krawiranda K, Kustosik N, Lisińska W, Rysz J, Franczyk B. Endothelial dysfunction as the common pathway linking obesity, hypertension and atherosclerosis. International Journal of Molecular Sciences. 2025; 26(20): 10096.
6.     McEniery CM, Yasmin n, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR, ACCT Investigators. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). Journal of the American College of Cardiology. 2005; 46(9): 1753–60.
7.     Niiranen TJ, McCabe EL, Larson MG, Henglin M, Lakdawala NK, Vasan RS, Cheng S. Heritability and risks associated with early onset hypertension: multigenerational, prospective analysis in the Framingham Heart Study. BMJ. 2017; 357.
8.     Fahs CA, Loenneke JP, Rossow LM, Tiebaud RS, Bemben MG. Methodological considerations for blood flow restricted resistance exercise. Journal of Trainology. 2012; 1(1): 14–22.
9.     Chase NL, Sui X, Lee D-c, Blair SN. The association of cardiorespiratory fitness and physical activity with incidence of hypertension in men. American Journal of Hypertension. 2009; 22(4): 417–24.
10.  Rodríguez S, Rodríguez-Jaime MF, León-Prieto C. Blood flow restriction training: physiological effects, molecular mechanisms, and clinical applications. Critical Reviews™ in Physical and Rehabilitation Medicine. 2024; 36(4).
11.  Cho C, Lee S. The effects of blood flow restriction aerobic exercise on body composition, muscle strength, blood biomarkers, and cardiovascular function: a narrative review. International Journal of Molecular Sciences. 2024; 25(17): 9274.
12.  Ferguson RA, Hunt JE, Lewis MP, Martin NR, Player DJ, Stangier C, Taylor CW, Turner MC. The acute angiogenic signalling response to low-load resistance exercise with blood flow restriction. European Journal of Sport Science. 2018; 18(3): 397–406.
13.  McIntosh MC, Mueller BJ, Tiede DR, Anglin DA, Kontos Jr GJ, Plotkin DL, Mattingly ML, Kontos NJ, Michel JM, Agyin-Birikorang A, Harrison K. Limited effects of dietary nitrate supplementation with resistance training on skeletal muscle and vascular outcomes in middle-aged and older adults. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2026; 330(2): R136–R50.
14.  Jiang H, Li L, Zhang L, Zang G, Sun Z, Wang Z. Role of endothelial cells in vascular calcification. Frontiers in Cardiovascular Medicine. 2022; 9: 895005.
15.  Moqimi R, Rajabi H, Sadegh Amani-Shalamzari S. The effect of four weeks resistance training along with blood flow restriction on the cross-sectional area of non-restricted muscles in active men. Journal of Practical Studies of Biosciences in Sport. 2022; 10(23): 20–30.
16.  ali Seyedi S, Khodaei K, Oranchuk D. The effects of low-intensity eccentric quasi-isometric training with blood flow restriction on serum levels of testosterone and cortisol, and on muscular hypertrophy and power in male athletes. Journal of Sport and Exercise Physiology. 2025; 18(4): 1-20.
17.  Vakili J, Nikookheslat S, Hassanlou FP. The effect of four weeks of resistance training with and without blood flow restriction on levels of anabolic and catabolic hormonal markers in middle-age sedentary males. Journal of Sport and Exercise Physiology. 2022; 15(1/45): 56.
18.  Apiwan M, Pudis M, Lertwanlop S, Wirakan S, Peeraporn N, Nattha M, Worrawut T. The Effects of Low-Load Resistance Training Combined with Blood Flow Restriction or Hypoxia on Cardiovascular Response: A Randomized Controlled Trial. Life. 2025; 15(8): 1162.
19.  Anabestani M, Hosseini-Kakhk A, Hamedinia M. Comparison of combined training with and without vascular occlusion on selected physical fitness components in postmenopausal women. Sport Physiology. 2014; 6(21): 123–36.
20.  Naserkhani F, Mehdizadeh R. The Acute Response of Hemodynamic Parameters to Walking on a Treadmill with Blood Flow Restriction in Sedentary Young Girls. Sport Physiology & Management Investigations. 2018; 9(4): 43–53.
21.  Larkin KA, Macneil RG, Dirain M, Sandesara B, Manini TM, Buford TW. Blood flow restriction enhances post–resistance exercise angiogenic gene expression. Medicine and Science in Sports and Exercise. 2012; 44(11): 2077.
22.  Drummond MJ, Fujita S, Takashi A, Dreyer HC, Volpi E, Rasmussen BB. Human muscle gene expression following resistance exercise and blood flow restriction. Medicine and Science in Sports and Exercise. 2008; 40(4): 691.
23.  Javad T-aJT-a, Khodaei K, Toloei-azar J. The Effect of Low-intensity TRX Suspension Training with Blood Flow Restriction on Serum Levels of Angiogenesis Factors VEGF, HIF-1, and Body Composition in Active Female. J Health Res Commun. 2024; 10 (2): 27-38.
24.  Rahmani K, Vakili J, Sari-Sarraf V. Comparison of the acute effects of specialized volleyball training with and without blood flow restriction (BFR) on CRP, ESR and TNF-α in adolescent female volleyball players. Journal of Sport and Exercise Physiology. 2025; 18(4): 42–55.
25.  Farhani F, Riyahi S. Comparison of three methods of resistance training with blood flow restriction on functional factors and cardio respiratory preparedness in military soldiers. Journal of Military Medicine. 2022; 21(1): 73–81.
26.  Karimi Ahmadabadi Z, Nemati J, Hesamuddin Mousavinia S, Rezaei R. Acute Effect of Single Bout Aerobic exercise with and without Blood Flow Restriction on Hemodynamic and Coagulation Indicators in Hypertension Disease. Journal of Sport and Exercise Physiology. 2022; 15(2): 52–63.
27.  Bazgir B, Valojerdi MR, Rajabi H, Fathi R, Ojaghi SM, Meybodi MKE, et al. Acute cardiovascular and hemodynamic responses to low intensity eccentric resistance exercise with blood flow restriction. Asian Journal of Sports Medicine. 2016; 7(4): e38458.
28.  Schamne JC, Motin C, Sochodolak RC, Lima-Silva AE, Okuno NM. Cardiac autonomic response to aerobic exercise with different levels of blood flow restriction in pre-hypertensive men. Sport Sciences for Health. 2021; 17(2): 375–82.
29.  Collier SR, Kanaley JA, Carhart R, Frechette V, Tobin MM, Hall AK, Luckenbaugh AN, Fernhall B. Effect of 4 weeks of aerobic or resistance exercise training on arterial stiffness, blood flow and blood pressure in pre-and stage-1 hypertensives. Journal of Human Hypertension. 2008; 22(10): 678–86.
30.  Warburton DE, Gledhill N, Jamnik VK. The Physical Activity Readiness Questionnaire (PAR-Q+) and Electronic Physical Activity Readiness Medical Examination (ePARmed-X+). Health Fit J Can. 2011; 4(2): 3–23.
31.  Azghandi S, Karami J, Sadeghi M. Investigation of the reliability and validity of the Persian version of the PAR-Q questionnaire for evaluating physical activity readiness. Iran J Sport Sci. 2008; 5(1): 27–36.
32.  Naderi M, Hosseini A, Ebrahimi M. Validation and reliability of the Persian PAR-Q questionnaire in the Iranian population.
J Sport Sci Res. 2014; 16(3): 85–94.
33.  Brzycki M. Strength predicting. A practical guide to grading resistance training. J Phys Educ Recreat Dance. 1993; 64(1): 88–90.
34.  Rolnick N, Kimbrell K, Cerqueira MS, Weatherford B, Brandner C. Perceived barriers to blood flow restriction training. Frontiers in Rehabilitation Sciences. 2021; 2: 697082.
35.  Loenneke J, Wilson J, Wilson G, Pujol T, Bemben M. Potential safety issues with blood flow restriction training. Scandinavian Journal of Medicine & Science in Sports. 2011; 21(4): 510–8.
36.  Fecchio RY, de Sousa JC, Oliveira-Silva L, da Silva Junior ND, Pio-Abreu A, da Silva GV, Drager LF, Low DA, Forjaz CL. Effects of dynamic, isometric and combined resistance training on blood pressure and its mechanisms in hypertensive men. Hypertension Research. 2023; 46(4): 1031–43.
37.  Zhao Y, Zheng Y, Ma X, Qiang L, Lin A, Zhou M. Low-intensity resistance exercise combined with blood flow restriction is more conducive to regulate blood pressure and autonomic nervous system in hypertension patients—compared with
high-intensity and low-intensity resistance exercise. Frontiers in Physiology. 2022; 13: 833809.
38.  Domingos E, Polito MD. Blood pressure response between resistance exercise with and without blood flow restriction:
A systematic review and meta-analysis. Life Sciences. 2018; 209: 122–31.
39.  Lopes KG, Farinatti P, Bottino DA, De Souza MDGC, Maranhão PA, Bouskela E, Lourenço RA, De Oliveira RB. Does resistance training with blood flow restriction affect blood pressure and cardiac autonomic modulation in older adults? International journal of Exercise Science. 2021; 14(3): 410.
40.  Brown M, Hudlicka O. Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: involvement of VEGF and metalloproteinases. Angiogenesis. 2003; 6(1): 1–14.
41.  Li S, Li S, Wang L, Quan H, Yu W, Li T, Li W. The effect of blood flow restriction exercise on angiogenesis-related factors in skeletal muscle among healthy adults: a systematic review and meta-analysis. Frontiers in Physiology. 2022; 13: 814965.
42.  Downs ME, Hackney KJ, Martin D, Caine TL, Cunningham D, O’Connor DP, Ploutz-Snyder LL. Acute vascular and cardiovascular responses to blood flow–restricted exercise. Medicine & Science in Sports & Exercise. 2014; 46(8): 1489–97.