214 https://oamjms.eu/index.php/mjms/index Scientifc Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2022 Jan 26; 10(A):214-219. https://doi.org/10.3889/oamjms.2022.8415 eISSN: 1857-9655 Category: A - Basic Sciences Section: Pathophysiology Wet Cupping’s Efect on Nitric Oxide Levels in Hypertensive Patients Sharlini Desfka 1,2 , Muhammad Ichwan 1,3 , Dedi Ardinata 1,4 * 1 Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; 2 Department of Physiology, Faculty of Medicine, Universitas Muhammadiyah Sumatera Utara, Medan, Indonesia; 3 Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia; 4 Department of Physiology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia Abstract BACKGROUND: Wet cupping is a non-pharmacological therapy that has been shown to assist hypertensive patients with blood pressure reduction. However, the underlying mechanisms by which wet-cupping lowers blood pressure are currently unknown. More scientifc investigation is necessary to explain the mechanism by which wet cupping lowers blood pressure, particularly the role of nitric oxide (NO). AIM: The study aimed to show the efect of wet cupping on NO levels in hypertensive patients. METHODS: A pre-experimental study using a single group pre-test and post-test design to monitor changes in blood NO levels and blood pressure in 45 hypertensive patients in Medan after 4 weeks of wet cupping therapy. The patients’ blood NO levels, as well as their systolic and diastolic blood pressures (SBP and DBP), were measured before and after 4 weeks of wet cupping. RESULTS: After 4 weeks of wet cupping, blood NO levels signifcantly increased (0.00704 mol/mL, p=0.039), while SBP and DBP levels signifcantly decreased (12.644 mmHg and 7.111 mmHg, respectively, p<0.001). However, there was no correlation between increased blood NO levels and reductions in SBP and DBP (p=0.468 and p=0.299, respectively). CONCLUSION: This study found that after 4 weeks of cupping therapy, the decrease in SBP and DBP was not accompanied by an increase in blood NO levels. Edited by: Sinisa Stojanoski Citation: Desfka S, Ichwan M, Ardinata D. Wet Cupping’s Efect on Nitric Oxide Levels in Hypertensive Patients. Open Access Maced J Med Sci. 2022 Jan 26; 10(A):214-219. https://doi.org/10.3889/oamjms.2022.8415 Keywords: Wet cupping; Nitric oxide; Blood pressure *Correspondence: Dedi Ardinata, Department of Physiology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia. E-mail: dedi1@usu.ac.id Received: 27-Dec-2021 Revised: 12-Jan-2022 Accepted: 16-Jan-2022 Copyright: © 2022 Sharlini Desfka, Muhammad Ichwan, Dedi Ardinata Funding: SD receives funding partially from the Faculty of Medicine, Universitas Muhammadiyah Sumatera Utara, Medan, Indonesia, in completing thesis research. Competing Interests: The authors have declared that no competing interests exist Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 International License (CC BY-NC 4.0) Introduction The World Health Organization (WHO) estimates that 1.4 billion people worldwide have high blood pressure [1]. The prevalence of hypertension suferers in Indonesia in 2018 reached 658,201 people (8.84%), North Sumatra province reached 41,382 people (6.07%), and the city of Medan reached 7174 people (5.17%) [2]. Physiological blood pressure regulation requires a complex interaction of several components of the integrated neurohumoral system, including the renin- angiotensin-aldosterone system (RAAS), natriuretic peptides, endothelium, sympathetic nervous system (SNS), and immune system. Disruption of the factors that control blood pressure in any component of this integrated neurohumoral system over time can cause an increase in mean blood pressure, blood pressure variability, or both, resulting in damage to target organs such as left ventricular hypertrophy and chronic renal failure, which can cause cardiovascular diseases [3]. Hypertension must be managed with both pharmacological and non-pharmacological therapy. Non- pharmacological therapy helps lower the daily dose of antihypertensive medications and delays the development of hypertension. Non-pharmacological therapy involves lifestyle changes, such as diet modifcation, exercise, stress avoidance, and alcohol consumption reduction [4]. One of the present non-pharmacological therapeutic approaches is complementary and alternative medicine (CAM), such as cupping [5]. Cupping has been shown to improve immunity by increasing the number of natural killers cells, lowering the clinical index of rheumatoid arthritis, and reducing the severity of fbromyalgia pain, headaches and migraines, and hypertension [6], [7], [8]. The benefts of wet cupping on hypertension have been demonstrated by a signifcant diference in systolic blood pressure (SBP) on day 42 after three sessions of wet cupping separated by 2 weeks in a group of hypertensive patients with no history of other chronic diseases [9]. Another study found that wet cupping was signifcantly efective in lowering blood pressure, both systolic and diastolic, in hypertensive patients at the 4 th week after wet cupping, which was performed 3 times on the 17 th , 19 th , and 21 st of the lunar calendar, while there was no signifcant diference at the 8 th week [10]. Wet cupping also afects baroreceptors, which are indicators of blood pressure decrease, as evidenced by a signifcant diference in systolic and diastolic blood pressure in hypertensive patients at