Effect of nitrate administration on plasma nitric oxide levels in patients with peripheral arterial disease at Dr. Sardjito General Hospital, Yogyakarta

https://doi.org/10.19106/JMedSci005304202105

Arditya Damarkusuma(1*), Muhamad Taufik Ismail(2), Hariadi Hariawan(3), Sherly Primasari Agus(4)

(1) Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta
(2) Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta
(3) Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta
(4) Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta
(*) Corresponding Author

Abstract


Peripheral arterial disease (PAD) is a disease involving reduction of blood flow to the inferior extremity associated with atherosclerotic lesions. In 2010, more than 200 million people with PAD were reported globally, including 54.8 million in Southeast Asia. The high prevalence of PAD causes its management become challenging for clinicians. Nitric oxide (NO) has a role in endothelial function that is associated with the appearance of symptoms in PAD patients. Exogenous nitrate is usually used as a primary vasodilator in the treatment of angina pectoris and Prinzmetal angina. However, information concerning the role of nitrate administration to improve symptomatic PAD patients is limited. This study aimed to evaluate the effectiveness of exogenous nitrates in increasing plasma NO levels and improving PAD patients. A prospective pre-post clinical trial involving PAD patients who were registered in the vascular registry at Dr. Sardjito General Hospital, Yogyakarta  was conducted. Primary endpoint was the change in plasma NO levels after short term administration of nitroglycerin oral 2.5 mg once daily (4 h) and long term (7 d). Analysis of variance test with Bonferroni posttest was used for statistical hypothesis testing. Among 33 subjects who completed this study, no negative side effects, and only one hypotensive patient was reported at the first follow-up after 4 h of the nitroglycerin administration. Plasma NO levels increased in the post 4 h and in the post 7 d administration. However, no statistically significant was observed (p > 0.05). Administration of exogenous nitrates in patients with PAD increases the plasma NO levels, even though it is not statistically significant.


Keywords


peripheral arterial disease; nitric oxide; acute limb ischemia; side effect; hypotension

Full Text:

PDF


References


  1. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Inteventional Radiology, and the ACC/AHA Task Force oc Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006; 113(11):e463-654. https://doi.org/10.1161/CIRCULATIONAHA.106.174526
  2. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res 2015; 116(9):1509-26. https://doi.org/10.1161/CIRCRESAHA.116.303849
  3. Creager M, Beckman J, Loscalzo J. Vascular medicine a companion to Braunwald’s heart disease, 2nd eds. Philadelphia: Elsevier Saunders, 2012; 880.
  4. Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013; 382(9901):1329-40. https://doi.org/10.1016/S0140-6736(13)61249-0
  5. International Diabetes Federation. IDF Diabetes Atlas, 6th eds. International Diabetes Federation. 2013.
  6. Infodatin. Situasi dan analisis diabetes. Jakarta Selatan: Kementerian Kesehatan RI Pusat Data dan Informasi, 2014.
  7. Criqui MH, Denenberg JO, Langer RD, Fronek A. The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med 1997; 2(3):221-6. https://doi.org/10.1177/1358863X9700200310
  8. Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease morbidity and mortality implications. Circulation 2006; 114(7):688-99. https://doi.org/10.1161/CIRCULATIONAHA.105.593442
  9. Kumar S, Singh RK, Bhardwaj TR. Therapeutic role of nitric oxide as emerging molecule. Biomed Pharmacother 2017; 85:182-201. https://doi.org/10.1016/j.biopha.2016.11.125
  10. Loffredo L, Carnevale R, Cangemi R, Angelico F, Augelletti T, Santo SD, et al. NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease. Int J Cardiol 2013; 165(1):184-92. https://doi.org/10.1016/j.ijcard.2012.01.069
  11. Lilly LS. Pathophysiology of Heart Disease, 5th eds. Philadelphia: Lippincott Williams & Wilkins. 2011.
  12. Lidder S, Webb AJ. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway. Br J Clin Pharmacol 2013; 75(3):677-96. https://doi.org/10.1111/j.1365-2125.2012.04420.x
  13. Katzung BG. Basic and clinical pharmacology, 10th eds. San Francisco: Mc Graw Hill Lange. 2006.
  14. Falconer D, Papageorgiou N, Salem K, Lim WY, Katsargyris A, Avgerinos E, et al. Nitric oxide donors for peripheral artery disease. Curr Opin Pharmacol 2018; 39:77-85. https://doi.org/10.1016/j.coph.2018.02.009
  15. Herman MG, Gardin JM, Jaff M, Mohler E, Roman M, Naqvi TZ. Guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology. Vasc Med 2006; 11(33):183-200. https://doi.org/10.1177/1358863x06070516
  16. Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, et al. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol (1985) 2011; 110(6):1582-91. https://doi.org/10.1152/japplphysiol.00071.2011
  17. Hiatt WR, Brass EP. Pathophysiology of peripheral artery disease, intermittent claudication, and critical limb ischemia. In: Creager MA, Beckman JA, Loscalzo J. editors. Vascular medicine: a companion to Braunwald's heart disease, 2nd eds. Philadelphia: W.B. Saunders. 2013.
  18. St-Pierre A, Cantin B, Lamarche B, Auger D, Després JP, Dagenais GR. Intermittent claudication: from its risk factors to its long-term prognosis in men. The Quebec Cardiovascular Study. Can J Cardiol 2010; 26(1):17-21. https://doi.org/10.1016/s0828-282x(10)70328-7
  19. Bauer TA, Regensteiner JG, Brass EP, Hiatt WR. Oxygen uptake kinetics during exercise are slowed in patients with peripheral arterial disease. J Appl Physiol (1985) 1999; 87(2):809-16. https://doi.org/10.1152/jappl.1999.87.2.809
  20. Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, Grobbee DE. Peripheral arterial disease in the elderly: The Rotterdam Study. Arterioscler Thromb Vasc Biol 1998; 18(2):185-92. https://doi.org/10.1161/01.atv.18.2.185
  21. Aboyans V, McClelland RL, Allison MA, McDermott MM, Blumenthal RS, Macura K, et al. Lower extremity peripheral artery disease in the absence of traditional risk factors. The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 2011; 214(1):169-73. https://doi.org/10.1016/j.atherosclerosis.2010.10.011
  22. Feron O, Dessy C, Moniotte S, Desager JP, Balligand JL. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 1999; 103(6):897-905. https://doi.org/10.1172/JCI4829
  23. de Berrazueta JR, Sampedro I, Garcia-Unzueta MT, Llorca J, Bustamante M, Amado JA. Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease. Am Heart J 2003; 146(4):E14. https://doi.org/10.1016/S0002-8703(03)00391-0



DOI: https://doi.org/10.19106/JMedSci005304202105

Article Metrics

Abstract views : 1309 | views : 1495


Bookmark and Share


Copyright (c) 2021 Arditya Damarkusuma, Muhamad Taufik Ismail, Hariadi Hariawan, Sherly Primasari Agus

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.