PLAT and endothelial dysfunction: Studies of endothelial dysfunction have reported evidence that the body’s production of endothelium-derived substances (e.g., nitric oxide, endothelin, angiotensin-converting enzyme, and tissue plasminogen activator) is altered after the ingestion of cigarette smoke.16 Free radicals that are either inhaled by the smoker or endogenously produced via xanthinoxidase, NADPH oxidase, or peroxidase enzymes initiate oxidative stress mechanisms.