Impact of nicotine on myocardial neutrophil uptake.
Excessive cigarette smoking is recognized as a major risk factor for ischemic heart disease. Although the mechanism by which smoking enhances this risk is not known, multiple lines of indirect evidence suggest that an adverse effect of nicotine on the interaction between neutrophils and the myocardium may play a central pathogenic role. Accordingly, this study employed an isolated rabbit heart preparation perfused at a constant flow rate with physiologic salt solution containing autologous neutrophils to test the hypotheses that nicotine promotes myocardial neutrophil uptake and that an augmented myocardial neutrophil burden intensifies the actions of stimulated neutrophils on the coronary circulation. Addition of 10(-7) M nicotine to the perfusion medium caused an abrupt and sustained sequestration of 111In-labeled neutrophils by isolated rabbit hearts. In contrast, preincubation of neutrophils in 10(-7) M nicotine without inclusion of the alkaloid in the perfusion medium failed to promote neutrophil uptake. Nicotine neither enhanced myocardial neutrophil sequestration induced by perfusion with hypoxic medium nor potentiated neutrophil chemotactic responses evoked by leukotriene B4, the putative mediator of hypoxia-induced myocardial neutrophil uptake. In addition, nicotine failed to influence either baseline levels or the hypoxia-induced accumulation of immunoreactive leukotriene B4 detected in myocardial biopsies. The inflammatory cell stimulant, formylmethionyl-leucyl-phenylalanine (fMLP), increased coronary vascular resistance in neutrophil-perfused hearts but not in hearts perfused with neutrophil-free medium. The magnitude of the fMLP-induced coronary response was augmented when the myocardial neutrophil burden was increased by the addition of nicotine to the perfusion medium or by perfusion with hypoxic medium. These observations suggest that nicotine promotes myocardial neutrophil uptake by mechanisms that do not relate to enhanced release and/or effects of endogenous leukotriene B4 and that sequestration of neutrophils intensifies their actions on the coronary circulation.
Owasoyo
J O
JO
College of Pharmacy, Division of Pharmacology, University of Kentucky, Lexington 40536-0082.
Jay
M
M
Gillespie
M N
MN
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D007975:Leukotriene B4 / Q000493:pharmacokinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009538:Nicotine / Q000633:toxicity*; D010477:Perfusion; D011817:Rabbits
D007975:Leukotriene B4; D009538:Nicotine