Combined acetaldehyde and nicotine exposure depresses cardiac contraction in ventricular myocytes: prevention by folic acid.
Chronic alcoholism can progress to alcoholic cardiomyopathy characterized by ventricular dilation and impaired ventricular contractility. Nicotine abuse continues to remain a serious risk factor for cardiovascular diseases. However, little is know regarding the combined effects. This study was designed to examine the role of short-term combined exposure of the main alcohol metabolite acetaldehyde (ACA) and nicotine on cardiac contractile function in adult rat ventricular myocytes, and if folate exposure attenuates the effect of ACA/nicotine. Mechanical and intracellular Ca2+ properties were evaluated by an IonOptix SoftEdge system. Short-term (4-6 h) culture of myocytes with ACA (10 microM), nicotine (100 microM), or combination of the two in sealed vials with silicone septa depressed maximal velocity of shortening/relengthening, without affecting duration of shortening/relengthening and intracellular Ca2+ handling. Interestingly, the toxin-induced defects on myocyte mechanical properties were ablated with cotreatment of folate (100 microM), an essential vitamin required for DNA synthesis and repair. Collectively, these data provided evidence that ACA and nicotine, either alone or in combination, directly depressed cardiomyocyte mechanical function possibly through mechanisms related to DNA damage.
Aberle
Nicholas S
NS
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Science, Grand Forks, ND 58203, USA.
Privratsky
Jamie R
JR
Burd
Larry
L
Ren
Jun
J
D000079:Acetaldehyde / Q000633:toxicity*; D000437:Alcoholism / Q000188:drug therapy; D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004338:Drug Combinations; D004347:Drug Interactions; D005492:Folic Acid / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004338:Drug Combinations; D009538:Nicotine; D005492:Folic Acid; D000079:Acetaldehyde; D002118:Calcium