Nicotine Without Combustion: Cardiovascular and Autonomic Effects of Replacement Therapies and Electronic Nicotine Delivery Systems.

INTRODUCTION: Nicotine is a highly addictive alkaloid that exerts significant cardiovascular and autonomic effects through activation of nicotinic cholinergic receptors, leading predominantly to sympathetic nervous system stimulation. This review synthesizes evidence on the cardiovascular impact of nicotine delivered via non-combustible routes, including Nicotine Replacement Therapies (NRT) and Electronic Nicotine Delivery Systems (ENDS). METHODS: A narrative literature review was conducted using major biomedical databases, focusing on studies published between 2000 and 2025 that evaluated autonomic regulation, hemodynamic responses, and vascular effects associated with nicotine exposure. RESULTS: The evidence consistently shows that nicotine, independent of the route of administration, increases heart rate, alters blood pressure, reduces heart rate variability, and disrupts sympathovagal balance, key markers of cardiovascular risk. DISCUSSION: While NRT provides controlled and predictable nicotine dosing with a relatively stable hemodynamic profile and remains an effective smoking cessation strategy, it is not devoid of cardiovascular effects, particularly when combined with ongoing nicotine use. In contrast, ENDS are characterized by substantial variability in nicotine delivery, greater oxidative stress, and more pronounced autonomic responses, raising concerns about their cardiovascular safety. CONCLUSION: Nicotine cannot be considered physiologically neutral for the cardiovascular system, underscoring the importance of distinguishing therapeutic from recreational nicotine use and the need for continued critical evaluation of emerging nicotine delivery products.