Nicotine exposure is increasingly widespread due to the expansion of the use of noncombustible tobacco and nicotine-replacement products; yet nicotine is still being framed as an addictive but relatively benign compound. This review synthesizes clinical and experimental evidence linking nicotine exposure to cardiorenal disease, emphasizing that risks persist after cessation. We discuss here a central novel concept that damage caused by nicotine in tissues is not determined solely by receptor signaling, as nicotine exists in chemical forms capable of strong receptor-independent membrane diffusion. Mechanistically, we highlight convergent pathways of nicotine-induced cellular injury, focusing on redox stress and underscoring major limitations in the field, such as the lack of studies in epithelial cells. We further emphasize the emerging paradigm that links nicotine and NOS biology, in which reduced nitric oxide bioavailability, NOS uncoupling, and peroxynitrite-mediated protein nitration represent underappreciated drivers of persistent cardiorenal injury in response to nicotine. Finally, we outline gaps and research priorities needed to identify therapeutic strategies that specifically mitigate nicotine-driven oxidative and nitrosative injury in vulnerable populations with hypertension, diabetes, and chronic kidney disease.
Semenikhina et al. (Fri,) studied this question.