تاثیر یک دوره تمرین مقاومتی به‌همراه محدودیت جریان خون بر عامل القای هایپوکسی، عامل رشد اندوتلیال عروقی و نیتریک اکساید در سالمندان

Extended Abstract
Background and Aim: Aging is a natural biological process accompanied by extensive physiological and metabolic alterations that contribute to a progressive decline in cardiovascular efficiency. Among these changes, endothelial dysfunction—considered an early indicator of vascular injury prior to structural alterations of the arterial wall—plays a key role in the pathogenesis of cardiovascular diseases. Key mediators of angiogenesis, such as hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF), are crucial for maintaining endothelial health and vascular adaptation. However, aging is associated with reduced expression of these genes and impaired endothelial function. Regular exercise training, particularly resistance training, has been identified as an effective non-pharmacological intervention to improve angiogenic signaling and endothelial activity in older adults. Recently, blood flow restriction (BFR) training has attracted attention as a novel, low-intensity method. In this approach, individuals can benefit from the advantages of resistance training using loads equivalent to 20–30% of one-repetition maximum (1RM), which would otherwise be insufficient to induce hypertrophy under normal conditions. However, based on the available evidence, few studies have investigated the effects of BFR training on angiogenesis indices in older adults. Considering the increasing prevalence of aging and cardiovascular disorders in this population, the identification of effective non-pharmacological interventions to enhance endothelial function is of great importance. Since many older adults are unable to perform high-intensity resistance exercises, BFR training may represent a novel, low-load approach capable of eliciting physiological adaptations similar to those induced by high-intensity training. Therefore, the present study aimed to examine the effect of 12 weeks of resistance training with and without BFR on serum levels of HIF-1α, VEGF, and nitric oxide (NO) in elderly individuals.
Materials and Methods: This study was a randomized controlled clinical trial with a pretest–posttest design. Following a public announcement at health centers in Zabol County, 45 elderly volunteers aged 60–70 years were selected through purposive convenience sampling and randomly assigned to three equal groups (n=15 each): resistance training, resistance training with BFR, and control. Inclusion criteria consisted of being healthy, aged between 60 and 70 years, and not using medications that could affect the study outcomes. Exclusion criteria included missing more than three training sessions or sustaining an injury, though no participants were excluded.
The intervention lasted 12 weeks, with two supervised sessions per week conducted in a gymnasium. Each session consisted of a 10-minute warm-up, a 50-minute main workout, and a 10-minute cool-down period. The resistance training group performed three lower-body exercises (horizontal leg press, leg extension, and leg curl). During the first four weeks, exercises were performed at 70% of 1RM for four sets of eight repetitions. In the second four weeks, intensity increased to 75% of 1RM and repetitions to 10. In the final four weeks, intensity reached 80% of 1RM with 12 repetitions.
In the BFR training group, the same three lower-body exercises were performed at an intensity of 20–30% of 1RM. The repetition pattern across four sets consisted of 30, 15, and 15 repetitions during the first, second, and third four-week phases, respectively.  Cuff pressure was set to 60% of limb occlusion pressure (LOP) in accordance with safety guidelines. Blood samples were obtained at baseline (pretest) and after 12 weeks (posttest) to assess serum levels of HIF-1α, VEGF, and NO. Statistical analyses were performed using analysis of covariance (ANCOVA) followed by LSD post hoc tests and the significance level was set at p≤0.05.
Findings: ANCOVA test revealed significant differences among the groups in mean levels of HIF-1α (F(2,41)=19.23, p=0.01, η²=0.81), VEGF (F(2,41)=85.45, p=0.01, η²=0.79), and NO (F(2,41)=38.31, p=0.01, η²=0.77). Post hoc analysis showed significant increases in HIF-1α (p=0.001), VEGF (p=0.01), and NO (p=0.01)  in both resistance and BFR training groups compared with the control group. Moreover, HIF-1α levels in the BFR group were significantly higher than those in the resistance training group (p=0.01). However, no significant differences were observed between the two training groups in VEGF (p=0.08) and NO (p=0.16) levels (Table 1).
Changes in diastolic blood pressure were not significant among the groups (F(2,41)=2.22, p=0.09, η²=0.05). However, a significant difference was observed in systolic blood pressure (F(2,41)=15.84, p=0.02, η²=0.39). Post hoc analysis revealed significant reductions in systolic blood pressure in both resistance and BFR groups compared with the control group (p=0.001), with no significant difference between the two training interventions (p=0.18).
Results revealed a significant difference in body weight among the study groups (F(2, 41)= 17.36, p=0.01, η²=0.49). Post hoc tests showed significant reductions in body weight in both resistance and BFR training groups compared to the control (p=0.01), with no significant difference between the two exercise groups (p=0.32).
Conclusion: The findings of the present study demonstrate that 12-week of resistance training, both in the traditional form and with BFR, led to significant increases in molecular indices related to hypoxia, including HIF-1α, VEGF, and NO, as well as a marked reduction in systolic blood pressure in older adults, while diastolic blood pressure showed no significant change. These results indicate that resistance training can effectively enhance vascular function during aging through the activation of hypoxia-related signaling pathways and improvement of endothelial function. Specially, the upregulation of HIF-1α and VEGF, as key factors in the angiogenic process, may contribute to increased capillary density and improved oxygen exchange efficiency in muscle tissues, whereas elevated NO levels promote vasodilation and reduce peripheral resistance. These physiological adaptations are presumably driven by the enhanced metabolic stress and transient hypoxic conditions elicited during training, which activate cellular signaling cascades related to angiogenic and vascular responses. Overall, the findings indicate that resistance training—especially when combined with BFR—can serve as a safe, practical, and effective non-pharmacological intervention to improve vascular health, mitigate age-related hypertension risk, and enhance the overall quality of life in older adults.
Ethical Considerations: This study was approved by the Ethics Committee of the University of Zabol (IR.UOZ.REC.1403.035) and registered in the Iranian Clinical Trials Center under the code IRCT20220322054338N4. All participants were informed about the study procedures and provided written informed consent.
Compliance with ethical guideline: The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and institutional guidelines. Participation was voluntary, and confidentiality of participant information was maintained.
Funding: This research was supported by the University of Zabol under grant number 0324.
Conflict of Interest: The authors declare no conflicts of interest regarding the publication of this study.