Effect of nicotine and nicotine metabolites on angiotensin-converting enzyme in human endothelial cells.
Nicotine has been shown to induce endothelial dysfunction, which is an early marker of atherosclerosis. Nicotine undergoes extensive metabolism in the liver, forming a number of major and minor metabolites. There are very limited data on the effect of nicotine metabolites on the cardiovascular system. This study investigates the effects of nicotine and the nicotine metabolites, cotinine, cotinine-N-oxide, nicotine-1'-N-oxide, norcotinine, trans-3'-hydroxycotinine, on angiotensin-converting enzyme (ACE) in human endothelial cells. Cultured endothelial cells obtained from human umbilical cord vein (HUVECs) were stimulated with nicotine or nicotine metabolites in concentrations similar to those observed in plasma during smoking. ACE activity and expression were analyzed using commercial kits. The results showed that nicotine and nicotine metabolites can increase both activity and expression of ACE. However, a marked individual variation in the response to the drugs was observed. This variation was not associated with the ACE insertion/deletion polymorphism. Tobacco contains numerous chemical compounds, and the underlying cause for development of atherosclerosis in smokers is probably multifactorial. The results from this study could explain one cellular mechanism by which smoking exerts negative effect on the vascular system.
Ljungberg
Liza U
LU
Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Persson
Karin
K
D050197:Atherosclerosis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D003367:Cotinine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000378:metabolism / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009538:Nicotine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D012907:Smoking / Q000009:adverse effects; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003497:Cyclic N-Oxides; D018722:Nicotinic Agonists; C066333:norcotinine; C001381:hydroxycotinine; C001605:cotinine-N-oxide; C024270:nicotine 1-N-oxide; D009538:Nicotine; D007703:Peptidyl-Dipeptidase A; D003367:Cotinine