Nicotine-associated cardiovascular dysfunction: From pharmacological insights to emerging therapeutic interventions.
Source: PubMed, NCBI / U.S. National Library of Medicine
Nicotine is a highly bioactive and addictive alkaloid that exerts prevalent cardiovascular and metabolic toxicity independent of other combustion-derived chemicals. Its rapid absorption and interaction with nicotinic acetylcholine receptors initiate a cascade of oxidative, inflammatory, and neuropharmacological responses that interrupt vascular, renal, and metabolic homeostasis. Nicotine triggers NADPH oxidase, mitochondrial dysfunction, and acid sphingomyelinase-ceramide signaling, resulting in reduced nitric oxide bioavailability, endothelial dysfunction, and lipid raft aggregation that promotes NLRP3 inflammasome activation. These mechanisms contribute to hypertension, atherosclerosis, arrhythmias, and heart failure through augmented oxidative stress, impaired vasodilation, sympathetic activation, and structural cardiac remodeling. Besides the cardiovascular system, nicotine disrupts lipid and glucose metabolism, induces podocyte injury, accelerates chronic kidney disease and promotes insulin resistance via inflammatory and redox-sensitive pathways. Understanding the molecular mechanisms driving nicotine toxicity is essential for developing targeted interventions. Emerging therapeutic strategies include pharmacotherapies for dependence, antihypertensive and lipid-lowering agents, metabolic modulators, antioxidants, and inhibitors of inflammasome or ceramide signaling. Overall, this review synthesizes current mechanistic and pharmacological evidence to clarify how nicotine
Abstract
Nicotine is a highly bioactive and addictive alkaloid that exerts prevalent cardiovascular and metabolic toxicity independent of other combustion-derived chemicals. Its rapid absorption and interaction with nicotinic acetylcholine receptors initiate a cascade of oxidative, inflammatory, and neuropharmacological responses that interrupt vascular, renal, and metabolic homeostasis. Nicotine triggers NADPH oxidase, mitochondrial dysfunction, and acid sphingomyelinase-ceramide signaling, resulting in reduced nitric oxide bioavailability, endothelial dysfunction, and lipid raft aggregation that promotes NLRP3 inflammasome activation. These mechanisms contribute to hypertension, atherosclerosis, arrhythmias, and heart failure through augmented oxidative stress, impaired vasodilation, sympathetic activation, and structural cardiac remodeling. Besides the cardiovascular system, nicotine disrupts lipid and glucose metabolism, induces podocyte injury, accelerates chronic kidney disease and promotes insulin resistance via inflammatory and redox-sensitive pathways. Understanding the molecular mechanisms driving nicotine toxicity is essential for developing targeted interventions. Emerging therapeutic strategies include pharmacotherapies for dependence, antihypertensive and lipid-lowering agents, metabolic modulators, antioxidants, and inhibitors of inflammasome or ceramide signaling. Overall, this review synthesizes current mechanistic and pharmacological evidence to clarify how nicotine contributes to cardiovascular and systemic disease and highlights the therapeutic opportunities to mitigate its increasing public health burden.