High-intensity interval training improves blood pressure and adropin plasma levels in elderly with hypertensive treatment

Document Type : Research Paper


Department of Exercise Physiology, Faculty of Sport Science and Health, University of Tehran


Background: Adropin is a newly identified bioactive protein that is important in energy hemostasis and vascular endothelial function.
Aim: The purpose of the present study was to investigate plasma levels of adropin and nitrite/nitrate (NO), in elderly treated hypertensive subjects at baseline and follow-up after 6 weeks of high-intensity interval training (HIIT).
Material and Methods: Forty-four elderly participants with treated hypertensives (age 61.09±5.82 years, 25 male and 19 female, BMI= 25.7±1.31 kg/m2) were randomly assigned to either the high-intensity interval training (HIIT) or control group. The HIIT group received an intervention consisting of 10 intervals of 1.5 min at 85% to 90% of their heart rate reserve (HRR), separated by 2 min of rest at 50% to 55% of their HRR, in three sessions per week for a duration of six weeks. Plasma levels of adropin and NO were measured using enzyme-linked immunosorbent assay. The statistical analysis was performed by two-way repeated ANOVA to determine differences between groups and Pearson’s correlation coefficient to determine correlation.
Results: The results showed that, following the six-week HIIT intervention, the plasma levels of adropin and NO significantly increased when compared to both control group (P= 0.0016) and the baseline (P= 0.0003) measurements. Peak oxygen consumption was increased after exercise training compared to the control group (P=0.005). Δ adropin in the HIIT group showed a positive correlation with increased Δ NO (r= 0.707, P= 0.002) and Δ VO2peak (r= 0.836, P= 0.001), and a negative correlation with Δ DBP (r= 0.643, P= 0.025) and Δ SBP (r= 0.691, P= 0.013).
Conclusions: The study findings suggests that HIIT can enhance both blood pressure and cardiorespiratory fitness. The observed increase in plasma level of adropin may have contributed to reduction of blood pressure by promoting nitric oxide production.


[1] Egan BM, Kjeldsen SE, Grassi G, Esler M, Mancia G. “The global burden of hypertension exceeds 1.4 billion people: should a systolic blood pressure target below 130 become the universal standard?”. J Hypertens. 2019; 37(6): 1148-53. https://doi.org/10.1097/hjh.0000000000002021.

[2] Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D'Agostino RB, et al. “Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study”. Jama. 2002; 287(8): 1003-10. https://doi.org/10.1001/jama.287.8.1003.

[3] Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. “Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.” Lancet. 2002; 360(9349): 1903-13. https://doi.org/10.1016/s0140-6736(02)11911-8.

[4] Kokkinos P, Manolis A, Pittaras A, Doumas M, Giannelou A, Panagiotakos DB, et al. “Exercise capacity and mortality in hypertensive men with and without additional risk factors”. Hypertension. 2009; 53(3): 494-9. https://doi.org/10.1161/hypertensionaha.108.127027.

[5] Faselis C, Doumas M, Kokkinos JP, Panagiotakos D, Kheirbek R, Sheriff HM, et al. “Exercise capacity and progression from prehypertension to hypertension”. Hypertension. 2012; 60(2): 333. https://doi.org/10.1161/hypertensionaha.112.196493.

[6] Ghardashi Afousi A, Izadi MR, Rakhshan K, Mafi F, Biglari S, Gandomkar Bagheri H. “Improved brachial artery shear patterns and increased flow-mediated dilatation after low-volume high-intensity interval training in type 2 diabetes”. Exp Physiol. 2018; 103(9): 1264-76. https://doi.org/10.1113/ep087005.

[7] Molmen-Hansen HE, Stolen T, Tjonna AE, Aamot IL, Ekeberg IS, Tyldum GA, et al. “Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients”. Eur J Prev Cardiol. 2012; 19(2): 151-60. https://doi.org/10.1177/1741826711400512.

[8] Izadi MR, Ghardashi Afousi A, Asvadi Fard M, Babaee Bigi MA. “High-intensity interval training lowers blood pressure and improves apelin and NOx plasma levels in older treated hypertensive individuals”. J Physiol Biochem. 2018; 74(1): 47-55. https://doi.org/10.1007/s13105-017-0602-0.

[9] Faselis C, Doumas M, Pittaras A, Narayan P, Myers J, Tsimploulis A, et al. “Exercise capacity and all-cause mortality in male veterans with hypertension aged ≥70 years”. Hypertension. 2014; 64(1): 30-5. https://doi.org/10.1161/hypertensionaha.114.03510.

[10] Byrkjeland R, Njerve IU, Arnesen H, Seljeflot I, Solheim S. “Reduced endothelial activation after exercise is associated with improved HbA(1c) in patients with type 2 diabetes and coronary artery disease”. Diab Vasc Dis Res. 2017; 14(2): 94-103. https://doi.org/10.1177/1479164116679077.

[11] Fujie S, Hasegawa N, Kurihara T, Sanada K, Hamaoka T, Iemitsu M. “Association between aerobic exercise training effects of serum adropin level, arterial stiffness, and adiposity in obese elderly adults”. Appl Physiol Nutr Metab. 2017; 42(1): 8-14. https://doi.org/10.1139/apnm-2016-0310.

[12] Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, Kalayci M, et al. “Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes”. Mol Cell Biochem. 2013; 380(1-2): 73-81. https://doi.org/10.1007/s11010-013-1660-4.

[13] Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, et al. “Adropin is a novel regulator of endothelial function”. Circulation. 2010; 122(11 Suppl): S185-92. https://doi.org/10.1161/circulationaha.109.931782.

[14] Wu L, Fang J, Chen L, Zhao Z, Luo Y, Lin C, et al. “Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients”. Clin Chem Lab Med. 2014; 52(5): 751-8. https://doi.org/10.1515/cclm-2013-0844

[15] Fujie S, Hasegawa N, Sato K, Fujita S, Sanada K, Hamaoka T, et al. “Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults”. Am J Physiol Heart Circ Physiol. 2015; 309(10): H1642-7. https://doi.org/10.1152/ajpheart.00338.2015.

[16] Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, et al. “Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study”. Circulation. 2007; 115(24): 3086-94. https://doi.org/10.1161/circulationaha.106.675041.

[17] Fujie S, Sato K, Miyamoto-Mikami E, Hasegawa N, Fujita S, Sanada K, Hamaoka T, Iemitsu M. “Reduction of arterial stiffness by exercise training is associated with increasing plasma apelin level in middle-aged and older adults”. PLoS One. 2014; 9(4): e93545. https://doi.org/10.1371/journal.pone.0093545.

[18] Haram PM, Kemi OJ, Lee SJ, Bendheim M, Al-Share QY, Waldum HL, et al. “Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity”. Cardiovasc Res. 2009; 81(4): 723-32. https://doi.org/10.1093/cvr/cvn332.

[19] Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, et al. “Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism”. Cell Metab. 2008; 8(6): 468-81. https://doi.org/10.1016/j.cmet.2008.10.011.

[20] Zhang H, Jiang L, Yang YJ, Ge RK, Zhou M, Hu H, et al. “Aerobic exercise improves endothelial function and serum adropin levels in obese adolescents independent of body weight loss”. Sci Rep. 2017; 7(1): 17717. https://doi.org/10.1038/s41598-017-18086-3.

[21] Fujie S, Hasegawa N, Horii N, Uchida M, Sanada K, Hamaoka T, et al. “Aerobic exercise restores aging-associated reductions in arterial adropin levels and improves adropin-induced nitric oxide-dependent vasorelaxation”. J Am Heart Assoc. 2021; 10(10): e020641. https://doi.org/10.1161/jaha.120.020641.

[22] Vázquez-Rey E, Kaski JC. “Cardiovascular syndrome X and endothelial dysfunction”. Rev Esp Cardiol. 2003; 56(2): 181-92. https://doi.org/10.1016/S0300-8932(03)76843-2.

[23] Ashor AW, Lara J, Siervo M, Celis-Morales C, Oggioni C, Jakovljevic DG, et al. Exercise modalities and endothelial function: a systematic review and dose-response meta-analysis of randomized controlled trials. Sports Med. 2015;45(2):279-96. https://doi.org/10.1007/s40279-014-0272-9.

[24] Madsen SM, Thorup AC, Overgaard K, Bjerre M, Jeppesen PB. “Functional and structural vascular adaptations following 8 weeks of low volume high intensity interval training in lower leg of type 2 diabetes patients and individuals at high risk of metabolic syndrome”. Arch Physiol Biochem. 2015; 121(5): 178-86. https://doi.org/10.3109/13813455.2015.1087033.

[25] Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, et al. “Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production”. Am J Physiol Heart Circ Physiol. 2005; 289(2): H813-22. https://doi.org/10.1152/ajpheart.00092.2005.