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This fatigue primarily arises from nicotine's stimulation of adrenaline release, resulting in increased heart rate and elevated blood pressure, which depletes energy reserves and consequently induces feelings of tiredness and drowsiness shortly after use

Subcutaneous or intraperitoneal injection of nicotine in male Wistar rats increased the level of serum corticosterone and inhibited the increase of nitric oxide produced by polymorphonuclear leukocytes (mainly TNF-), thus inhibiting the plasma exudation caused by passive skin reaction (Kubo et al., 2003