NITROGLYCERINE IN CONTEMPORARY CARDIOVASCULAR THERAPEUTICS: MOLECULAR MECHANISMS, CLINICAL APPLICATIONS, AND FUTURE PERSPECTIVES

Abstract

Nitroglycerine (glyceryl trinitrate) remains one of the most extensively utilized vasodilators in cardiovascular medicine, with a therapeutic legacy spanning over 150 years. Despite the emergence of novel anti-anginal and heart failure therapies, nitroglycerine continues to serve as a cornerstone agent for rapid symptomatic relief in angina pectoris and acute coronary syndromes. This review provides a comprehensive and mechanistically integrated analysis of nitroglycerine, encompassing its chemical characteristics, pharmacokinetic profile, nitric oxide–mediated signaling pathways, hemodynamic effects, clinical indications, adverse effects, drug interactions, and the phenomenon of nitrate tolerance. Particular emphasis is placed on mitochondrial aldehyde dehydrogenase (ALDH2)- dependent bioactivation, cyclic guanosine monophosphate (cGMP) signaling, and emerging insights into pharmacogenomic variability influencing therapeutic response. Contemporary clinical applications in acute coronary syndromes, hypertensive emergencies, pulmonary edema, perioperative blood pressure control, and special populations are critically examined alongside limitations related to tachyphylaxis and long-term efficacy. Furthermore, evolving research directions, including nanoformulations, sustained-release delivery systems, and comparative effectiveness against newer anti-anginal agents, are discussed to contextualize the modern relevance of this classical therapy. While nitroglycerine does not confer demonstrated mortality benefit in chronic coronary disease, its rapid onset of action and predictable hemodynamic profile sustain its indispensable role in acute cardiovascular care. Ongoing translational research aimed at optimizing delivery strategies and overcoming tolerance mechanisms may further refine its clinical utility in contemporary cardiovascular therapeutics.