CRCardiovascular Reviews3083-48802981-8109Bio-Byword Scientific Publishing Pty. Ltd.10.26689/cr.v2i4.9346ArticleAdvances in Identification and Clinical Management Strategies of Nitrate Resistancehttps://artdesignp.com/journal/CR/2/4/10.26689/cr.v2i4.9346ZhaoZheng,ZhangQingshan,SunLi,FengXue,LiXiaolu2025242025-01-13Nitrates are widely used in acute and critical diseases such as angina pectoris, acute heart failure and hypertension. However, there are still many problems caused by the non-standard use of these kinds of drugs and drug resistance, which need to be paid attention to in clinical practice, scientific research, and patient education. This article mainly reviews the identification and clinical treatment strategies for nitrate resistance.

Thadani U, Whitsett T, Hamilton SF, 1988, Nitrate Therapy for Myocardial Ischemic Syndromes: Current Perspectives Including Tolerance. Current Problems in Cardiology, 1988: 25–784.

Munzel T, Giaid A, Kurz S, et al., 1995, Evidence for a Role of Endothelin 1 and Protein Kinase C in Nitroglycerin Tolerance. Proceedings of the National Academy of Sciences of the United States of America, 92: 5244–5248.

Bengt WJ, 1986, Nitrate Therapy Today. Acta Pharmacologica et Toxicologica, 59(5): 7–16.

Daiber A, Gori T, 2010, Mechanismen und Klinischer Stellenwert der Nitrattoleranz. Pharmazie in unserer Zeit, 39(5): 375–384.

Daiber A, Munzel T, Gori T, 2010, Organic Nitrates and Nitrate Tolerance—State of the Art and Future Developments. Advances in Pharmacology, 60: 177–227.

Heitzer T, Just H, Brockhoff C, et al., 1998, Long-Term Nitroglycerin Treatment Is Associated with Supersensitivity to Vasoconstrictors in Men with Stable Coronary Artery Disease: Prevention by Concomitant Treatment with Captopril. Journal of the American College of Cardiology, 31: 83–88.

Parker JO, Parker JD, 1992, Neurohormonal Activation During Nitrate Therapy: A Possible Mechanism for Tolerance. The American Journal of Cardiology, 70: 93B–97B.

Larson HN, Zhou J, Chen Z, et al., 2007, Structural and Functional Consequences of Coenzyme Binding to the Inactive Asian Variant of Mitochondrial Aldehyde Dehydrogenase: Roles of Residues 475 and 487. Journal of Biological Chemistry, 282(17): 12940–12950.

Munzel T, Daiber A, Gori T, 2011, Nitrate Therapy: New Aspects Concerning Molecular Action and Tolerance. Circulation, 123: 2132–2144.

Han Y, Dalin J, Fei X, 2016, Advances in Evaluation Methods of Drug Resistance to Nitrates. Modern Medicine and Clinical Medicine, 31(5): 723–726.

Amsterdam EA, 1992, Rationale for Intermittent Nitrate Therapy. The American Journal of Cardiology, 70: 55–60.

Fang L, 2017, Drug Resistance and Clinical Countermeasures of Nitrates. Chinese Medicine Guide, 15(3): 297–298.

Chen Y, Yu X, 2019, Identification and Management of Emergency Patients with Low Reaction or Resistance to Nitrates. Chinese Journal of Emergency Medicine, 31(9): 1174–1181.

Kosmicki MA, Szwed H, Sadowski Z, 2004, Anti-Ischemic Response to Sublingual Nitroglycerin During Oral Administration of Isosorbide Dinitrate in Patients with Stable Angina Pectoris: When Does Cross-Tolerance Occur? Cardiovascular Drugs and Therapy, 18: 47–55.

Miura T, Nishinaka T, Terada T, et al., 2017, Vasodilatory Effect of Nitroglycerin in Japanese Subjects with Different Aldehyde Dehydrogenase 2 (ALDH2) Genotypes. Chemico-Biological Interactions, 276: 40–45.

Li Y, Zhang D, Jin W, et al., 2006, Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism Contributes to the Variation in Efficacy of Sublingual Nitroglycerin. Journal of Clinical Investigation, 116(2): 506–511.

Xia JQ, Song J, Zhang Y, et al., 2015, Effect of Aldehyde Dehydrogenase 2 Gene Polymorphism on Hemodynamics After Nitroglycerin Intervention in Northern Chinese Han Population. Chinese Medical Journal, 128(2): 180–185.

Shin MJ, Cho Y, Davey SG, 2017, Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea. Yonsei Medical Journal, 58(4): 689–696.

Millwood IY, Walters RG, Mei XW, et al., 2019, Conventional and Genetic Evidence on Alcohol and Vascular Disease Aetiology: A Prospective Study of 500,000 Men and Women in China. Lancet, 393(10183): 1831–1842.

Goedde HW, Agarwal DP, Harada S, et al., 1986, Aldehyde Dehydrogenase Polymorphism in North American, South American, and Mexican Indian Populations. American Journal of Human Genetics, 38(3): 395–399.