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1 Departments of Surgery, 2 Physiology and Biophysics, 3 Internal Medicine, and the 4 Nicotine Research Center, Mayo Clinic and Foundation, Rochester, Minnesota 55905
Nicotine patches are available as an over-the-counter
medication for aid in smoking cessation. This study was designed to determine how nicotine patch therapy over time and dose ranges used in
smoking cessation programs in humans affects endothelium-dependent relaxations. Dogs were treated with nicotine patches (11, 22, or 44 mg/day) for 2 and 5 wk. Circulating nicotine and oxidized products of
nitric oxide (NOx) were measured. Coronary arteries were prepared for
measurement of isometric force and aortic endothelial cells were
prepared for measurement of mRNA or NO synthase (NOS) activity.
Circulating nicotine increased with increasing concentrations of
nicotine patches. After 5 wk of treatment with 22 mg/day patches, circulating NOx was reduced but NOS activity was increased. NOS mRNA
was similar among groups. Only after 5 wk of treatment with 22 mg/day
patches were endothelium-dependent relaxations reduced to
2-adrenergic agonists, ADP, and the calcium ionophore
A-23187. These results suggest a time and biphasic dose effect of
nicotine treatment on endothelium-dependent responses that may be
related to bioavailability of NO. This complex relationship of duration and dose of nicotine treatment may explain, in part, discrepancies in
effects of nicotine on endothelium-dependent responses.
canine; coronary artery; nitric oxide; nitric oxide synthase
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