title: Nicotine inhibits cardiac apoptosis induced by lipopolysaccharide in rats.
abstract: OBJECTIVE
  Apoptosis develops in several heart diseases, but the therapeutic options are limited. It was hypothesized that nicotine, which inhibits apoptosis in several cells, inhibits cardiac apoptosis induced by lipopolysaccharide (LPS).
  
  
  BACKGROUND
  Over-the-counter nicotine produces sustained levels (10 to 25 ng/ml) that may be antiapoptotic. Low levels of LPS induce apoptosis by activating tissue renin-angiotensin to stimulate angiotensin II, type 1 (AT(1)) receptors in cardiac myocytes.
  
  
  METHODS
  Adult Sprague Dawley rats were pretreated with nicotine (6 mg/kg/day) or saline for seven to ten days (miniosmotic pumps). The LPS (1 mg/kg) was injected intravenously. Toll-like receptor 4 (TLR4) and angiotensinogen messenger ribonucleic acid (mRNA) were measured in the heart after 0, 4, 8, 16, and 24 h. Cardiac apoptosis was measured by terminal deoxy-nucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining after 24 h. In vitro effects of LPS (10 ng/ml, 24 h) were studied in cardiac myocytes isolated from rats pretreated with nicotine for 7 to 10 days, or after pre-exposing myocytes to nicotine (15 ng/ml) for 1, 4, 16, or 24 h.
  
  
  RESULTS
  Neither nicotine nor LPS affected systolic blood pressure. The LPS increased cardiac apoptosis after 24 h in saline-treated, but not nicotine-treated rats, despite similar increases in cardiac TLR4 and angiotensinogen mRNA over 8 to 16 h. The LPS-induced apoptosis was blocked by pre-exposing myocytes to nicotine for 4 to 24 h (partial inhibition after 1 h). Nicotine did not inhibit apoptosis induced by angiotensin II (100 nM, 24 h).
  
  
  CONCLUSIONS
  Therapeutic levels of nicotine inhibit LPS-induced cardiac apoptosis. This occurs after LPS increases TLR4 and angiotensinogen mRNA, but proximal to AT(1) receptor activation. Nicotine may be a novel inhibitor of cardiac apoptosis in conditions associated with circulating LPS (e.g., decompensated heart failure, acute and chronic infections).
authors.affiliation: Cardiology Section, Department of Medicine, V.A. San Diego Healthcare System and University of California, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Evelyn
authors.initials: E
authors.lastname: Bayna
authors.forename: Erminia
authors.initials: E
authors.lastname: Dalle Molle
authors.forename: Wilbur Y W
authors.initials: WY
authors.lastname: Lew
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D006331:Heart Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D005731:Ganglionic Stimulants; D008070:Lipopolysaccharides; D009538:Nicotine