Exaggerated nicotine-induced norepinephrine release from atherosclerotic rabbit hearts.

Excessive cigarette smoking acts synergistically with atheromatous coronary artery disease to greatly enhance the risk of acute myocardial infarction. To explore a possible mechanism of this relation, the present study tested the hypotheses that diet-induced atherosclerosis in rabbits is associated with an increase in myocardial (-)-norepinephrine content and that the increased (-)-norepinephrine can be released by nicotine. Adult male rabbits were rendered atherosclerotic by feeding them a standard laboratory diet enriched with 2% cholesterol. After 12-13 weeks on the diet, hearts were excised and retroperfused according to the Langendorff technique. There were no differences between control and atherosclerotic animals in terms of baseline (-)-norepinephrine concentration in the coronary effluent. However, increases in effluent (-)-norepinephrine concentration provoked by 10 micrograms and 30 micrograms nicotine were significantly greater in atherosclerotic hearts than in controls. Similarly, myocardial tissue from atherosclerotic animals contained significantly more (-)-norepinephrine than controls. These observations suggest that diet-induced atherosclerosis in rabbits is associated with an increase in myocardial (-)-norepinephrine content and that the augmented (-)-norepinephrine pool can be mobilized by nicotine.