Adolescent nicotine exposure alters cardiac autonomic responsiveness: beta-adrenergic and m2-muscarinic receptors and their linkage to adenylyl cyclase

Recent work indicates that adolescent smokers have an abnormally high incid ence of heart rate irregularities. In the current study, adolescent rats re ceived nicotine by continuous infusion from postnatal days (PN) 30-47.5, us ing a regimen designed to produce plasma levels found in smokers. We then a ssessed the levels of cardiac beta-adrenergic and m2-muscarinic cholinergic receptor binding, and receptor linkages to adenylyl cyclase activity, duri ng nicotine exposure and for 1 month afterwards. In the nicotine-exposed gr oup, m2-receptors showed a significant reduction that persisted through PN7 5, 1 month after the termination of treatment. beta-Receptors showed a tend ency toward initial suppression and subsequent elevation. The receptor chan ges were accompanied by corresponding alterations in the response of adenyl yl cyclase to carbachol and isoproterenol: the inhibitory muscarinic respon se was reduced, so that the net response to combined treatment with carbach ol and isoproterenol was enhanced. There were additional changes in basal a nd forskolin-Mn2+ -stimulated adenylyl cyclase activity suggestive of shift s in enzymatic catalytic properties. The effects of adolescent nicotine exp osure were distinct from those seen previously with fetal nicotine treatmen t. In light of the worldwide increase in tobacco use by teenagers, these st udies raise concern that cardiovascular function may be especially vulnerab le during this critical period. (C) 2000 Elsevier Science B.V. All rights r eserved.