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 incidence of heart rate irregularities. In the current study, adolescent rats received nicotine by continuous infusion from postnatal days (PN) 30-47.5, using a regimen designed to produce plasma levels found in smokers. We then assessed the levels of cardiac beta-adrenergic and m2-muscarinic cholinergic receptor binding, and receptor linkages to adenylyl cyclase activity, during nicotine exposure and for 1 month afterwards. In the nicotine-exposed group, m2-receptors showed a significant reduction that persisted through PN75, 1 month after the termination of treatment. beta-Receptors showed a tendency toward initial suppression and subsequent elevation. The receptor changes were accompanied by corresponding alterations in the response of adenylyl cyclase to carbachol and isoproterenol: the inhibitory muscarinic response was reduced, so that the net response to combined treatment with carbachol and isoproterenol was enhanced. There were additional changes in basal and forskolin-Mn(2+)-stimulated adenylyl cyclase activity suggestive of shifts in enzymatic catalytic properties. The effects of adolescent nicotine exposure were distinct from those seen previously with fetal nicotine treatment. In light of the worldwide increase in tobacco use by teenagers, these studies raise concern that cardiovascular function may be especially vulnerable during this critical period.
Chow
F A
FA
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Seidler
F J
FJ
McCook
E C
EC
Slotkin
T A
TA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D043585:Receptor, Muscarinic M2; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D005576:Colforsin; D008345:Manganese; D009538:Nicotine; D002217:Carbachol; D000262:Adenylyl Cyclases; D007545:Isoproterenol