Short-term treatment with transdermal nicotine affects the function of canine saphenous veins

Experiments were designed to determine the effects of nicotine treatment on the functions of saphenous veins used for coronary artery bypass grafts in dogs. Dogs received either no treatment or transdermal nicotine for 5 week s at doses of 11 mg, 22 mg or 44 mg/day. Saphenous veins were removed and s uspended for the measurement of isometric force in organ chambers. Endothel ium was removed mechanically from some rings. N-G-mono-methyl-L-arginine (L -NMMA; 10(-4) M) was used to inhibit the production of nitric oxide. Contra ctions to alpha(2)-adrenergic stimulation were decreased in veins from dogs treated with a 22-mg/day dose of transdermal nicotine. In addition, endoth elium-dependent relaxations to adenosine-diphosphate (10(-8)10(-4) M) and t he calcium ionophore A23,187 (10(-8)-10(-6) M) were decreased in veins from dogs with a 22-mg/day dose and increased in veins from dogs treated with a 44-mg/day dose. These relaxations were inhibited by L-NMMA. Plasma concent rations of oxidized products of nitric oxide were decreased only in dogs tr eated with 22 mg/day of nicotine. The relaxation of rings without endotheli um (direct response on the smooth muscle) to nitric oxide were not altered by nicotine treatment. These results suggest that the short-term treatment of dogs with intermediate (22 mg/day) but not low (11 mg/day) or high (44 m g/day) doses of transdermal nicotine decreases the endothelial function of veins used for coronary artery bypass grafts. Therefore, changes in plasma products of nitric oxide and endothelium-dependent relaxations mediated by nitric oxide are related to the dose of nicotine treatment.