title: Endothelin-1 as a potential marker of melatonin's therapeutic effects in smoking-induced vasculopathy.
abstract: OBJECTIVE
  Smoking is a significant independent risk factor for cardiovascular disease. Among the chemicals present in the cigarette smoke, nicotine is responsible for much of the damage; it induces marked vessel morphological dysfunction and vasoconstriction. Unfortunately, pharmacological or behavioural treatment is not useful against cigarette smoking. The purpose of this study is to test, in experimental conditions, the therapeutic ability of exogenous melatonin administered after smoking-induced vasculopathy and to evaluate the targets of its effects.
  
  
  METHODS
  Nicotine was orally administered for 28 days. Thereafter, the rats were orally treated with melatonin for another 28 days. Vessel damage, an important vasoconstrictor peptide (endothelin-1) and the oxidative stress markers were analysed.
  
  
  RESULTS
  Nicotine treatment induced marked endothelial damage and an obvious vasoconstriction in the aorta as evaluated by an increased endothelin-1 (ET-1) expression. These alterations were correlated with a reduction of endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) and with increases of heat shock protein (Hsp70) and inducible nitric oxide synthase (iNOS) activities. Melatonin not only improved the impairment of endothelial-dependent relaxation, but also induced the increase of eNOS and SOD and the reduction of iNOS and Hsp70.
  
  
  CONCLUSIONS
  The findings indicate that nicotine is associated with an elevated synthesis of the vasoconstrictor peptide (ET-1); it also induces a reduction of nitric oxide-mediated vasodilatation (eNOS) and promotes oxidative stress in the vessel wall. We propose that melatonin should be considered as a therapeutic intervention for smokers since it reduces vasoconstriction and oxidative stress and improves endothelial physiology.
authors.affiliation: Department of Biomedical Science and Biotechnology, Section of Human Anatomy, University of Brescia, Viale Europa 11, Brescia, Italy.
authors.forename: Luigi Fabrizio
authors.initials: LF
authors.lastname: Rodella
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.forename: Claudia
authors.initials: C
authors.lastname: Rossini
authors.forename: Eleonora
authors.initials: E
authors.lastname: Foglio
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D019332:Endothelin-1 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D009538:Nicotine / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D018840:HSP70 Heat-Shock Proteins; D009538:Nicotine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008550:Melatonin