Nicotine-induced calcium overload during postischemic reperfusion.
The excessive gain in Ca2+ that occurs when hearts are reperfused after prolonged periods of ischemia contributes to cell death and tissue necrosis. The following experiments were undertaken to determine whether nicotine, in a concentration equivalent to the peak concentration present in plasma after cigarette smoke inhalation, alters reperfusion-induced Ca2+ gain in isolated rat hearts. Nicotine (0.15 microgram/ml) failed to increase tissue Ca2+ during aerobic perfusion but increased Ca2+ gain during reperfusion after 30 (p less than 0.02) or 60 (p less than 0.02) min of normothermic ischemia. The increase of Ca2+ gain was independent of a nicotine-induced release of norepinephrine (NE) or an altered "reflow area", heart rate, force of contraction, or end-diastolic resting tension. Pretreatment for 3 days with anipamil (20 mg/kg), a long-acting calcium channel blocker, attenuated the reperfusion-induced Ca2+ gain after 30 min of global ischemia, and reduced (p less than 0.001) the nicotine-induced exacerbation of that gain, without altering tissue ATP or creatine phosphate (CP). Verapamil (1 X 10(-6) M) reduced (p less than 0.02) the nicotine-induced exacerbation of Ca2+ gain caused by reperfusion after 30 min of ischemia.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009538:Nicotine / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000032:analysis; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D011437:Propylamines; D010725:Phosphocreatine; D009538:Nicotine; D000255:Adenosine Triphosphate; C045313:anipamil; D002118:Calcium; D009638:Norepinephrine